2,677 results match your criteria Differentiation [Journal]


Hepatic differentiation of human pluripotent stem cells by developmental stage-related metabolomics products.

Differentiation 2019 Jan 28;105:54-70. Epub 2019 Jan 28.

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Diabetes Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Irwin S. and Sylvia Chanin Institute for Cancer Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address:

Endogenous cell signals regulate tissue homeostasis and are significant for directing the fate of stem cells. During liver development, cytokines released from various cell types are critical for stem/progenitor cell differentiation and lineage expansions. To determine mechanisms in these stage-specific lineage interactions, we modeled potential effects of soluble signals derived from immortalized human fetal liver parenchymal cells on stem cells, including embryonic and induced pluripotent stem cells. Read More

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http://dx.doi.org/10.1016/j.diff.2019.01.005DOI Listing
January 2019

Wnt signaling in intestinal inflammation.

Differentiation 2019 Jan 24. Epub 2019 Jan 24.

Wallenberg Centre for Molecular Medicine (WCMM), Linköping University, S-581 85 Linköping, Sweden; Department of Clinical and Experimental Medicine (IKE), Faculty of Health Sciences, Linköping University, S-581 85 Linköping, Sweden. Electronic address:

Chronic inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are a major health burden worldwide. Numerous conserved signaling pathways control tissue injury and repair during colitis, but owing to the complexity of the inflammatory process, their individual contribution remains poorly understood. A key regulatory pathway in the intestinal mucosa is Wnt/β-catenin signaling, which acts as the central organizer of epithelial stem cell identity and maintenance. Read More

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http://dx.doi.org/10.1016/j.diff.2019.01.002DOI Listing
January 2019
4 Reads

Assessment of iPSC teratogenicity throughout directed differentiation toward an alveolar-like phenotype.

Differentiation 2019 Jan 24;105:45-53. Epub 2019 Jan 24.

Department of Pediatrics, University of Connecticut Health Center, Farmington, CT, USA; Department of Surgery, Connecticut Children's Medical Center, Hartford, CT, USA. Electronic address:

Considerable work has gone into creating cell therapies from induced pluripotent stem cells (iPSCs) since their discovery just over a decade ago. However, comparatively little research has been done concerning the safety of iPSCs and their progeny and specifically the mechanisms governing teratogenicity. The aim of this study was to ascertain at what developmental phase iPSCs undergoing differentiation to an alveolar-like phenotype lose their capacity to form a teratoma and uncover potential mechanisms responsible. Read More

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http://dx.doi.org/10.1016/j.diff.2019.01.003DOI Listing
January 2019

A contemporary snapshot of intestinal stem cells and their regulation.

Differentiation 2019 Jan 25. Epub 2019 Jan 25.

A⁎STAR Institute of Medical Biology, 138648 Singapore, Singapore; Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan; Centre for Regenerative Medicine, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK; School of Biological Sciences, Nanyang Technological University, Singapore 308232, Singapore. Electronic address:

Intestinal stem cells (ISCs) marked by Lgr5 are located at the bottom of the epithelial crypt compartment. Canonical Wnt signaling, activated by Wnt/Rspo ligands, determines the stem cell identity of Lgr5 + ISCs and is strictly regulated by the ISC niche. Emerging evidence indicates that both epithelial and stromal compartments provide the requisite Wnt/Rspo ligands, confining the ISC niche to the lower crypt regions of the intestine. Read More

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http://dx.doi.org/10.1016/j.diff.2019.01.004DOI Listing
January 2019

Stromal control of intestinal development and the stem cell niche.

Differentiation 2019 Jan 8. Epub 2019 Jan 8.

Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 169857 Singapore, Singapore; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27703, USA. Electronic address:

Intestinal homeostasis is dependent on the continuous production of differentiated epithelial cells from a sustainable and resilient stem cell compartment. Wnt/β-catenin signaling plays a central role in this process, cooperating with R-spondins, growth factors and regulators of the TGF-β/BMP pathway to generate a specialized tissue microenvironment that regulates the intestinal stem cell niche. Recent studies revealed that many of these factors are produced in a paracrine manner by specialized cell populations that reside in the subepithelial stroma. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03014681183017
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http://dx.doi.org/10.1016/j.diff.2019.01.001DOI Listing
January 2019
3 Reads

Connexin 43 is involved in early differentiation of human embryonic stem cells.

Differentiation 2018 Dec 19;105:33-44. Epub 2018 Dec 19.

Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong SAR, China; Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong Shenzhen Hospital, Shenzhen, China. Electronic address:

Gap junctional intercellular communication (GJIC) is important for maintaining the pluripotency of mouse embryonic stem cells (mESC). However, human ESC (hESC) have a high level of connexin (Cx) molecules with unknown function. In this study, we found that the major Cx molecule, Cx43, was highly expressed in undifferentiated hESC. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03014681183014
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http://dx.doi.org/10.1016/j.diff.2018.12.003DOI Listing
December 2018
6 Reads

Phospholipase A2 products predict the hematopoietic support capacity of horse serum.

Differentiation 2018 Dec 6;105:27-32. Epub 2018 Dec 6.

Department of Hematology and Oncology, Medical Faculty, University of Leipzig, Leipzig, Germany.

Horse serum is commonly used as an additive to support the maintenance of hematopoietic progenitor cells in culture. However, the wide variability in the performance of different lots calls for parallel testing of multiple batches over extended periods of culture. Identification of the serum components that determine hematopoietic support would therefore save considerable time and effort and would help to standardize culture procedures. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03014681183010
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http://dx.doi.org/10.1016/j.diff.2018.12.002DOI Listing
December 2018
10 Reads

Mesenchymal stromal cells isolated from human fetal liver release soluble factors with a potential role in liver tissue repair.

Differentiation 2018 Dec 5;105:14-26. Epub 2018 Dec 5.

Department of Research, IRCCS-ISMETT, Palermo, Italy.

We isolated a population of proliferating cells from cultured human fetal hepatocytes of 16-22 weeks gestational age. The cells shared a similar phenotype to that of mesenchymal stromal cells (MSCs) according to the International Society for Cellular Therapy (ISCT), including plastic adherence, antigen expression profile, and in vitro multilineage differentiation potential. Fetal liver (FL)-MSCs expressed the albumin gene, and harbored a subpopulation of CK18 cells (20-40%), which defined their hepatic origin. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03014681183012
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http://dx.doi.org/10.1016/j.diff.2018.12.001DOI Listing
December 2018
11 Reads

Fractionation of embryonic cardiac progenitor cells and evaluation of their differentiation potential.

Differentiation 2018 Nov 23;105:1-13. Epub 2018 Nov 23.

Department of Pharmacology, Dalhousie University, Sir Charles Tupper Building, 5850 College Street, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2. Electronic address:

Mid-gestation mouse ventricles (E11.5) contain a larger number of Nkx2.5 cardiac progenitor cells (CPCs). Read More

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http://dx.doi.org/10.1016/j.diff.2018.11.001DOI Listing
November 2018
2 Reads

Designer macrophages: Pitfalls and opportunities for modelling macrophage phenotypes from pluripotent stem cells.

Differentiation 2018 Nov - Dec;104:42-49. Epub 2018 Oct 16.

The Centre for Stem Cell Systems, MDHS, University of Melbourne, Parkville, Victoria 3010, Australia; The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3010, Australia. Electronic address:

Macrophages are phagocytic immune cells resident in every tissue that are not only important for host defence, but are also involved in tissue homeostasis, injury, and disease. Despite increasingly sophisticated methods for in vitro macrophage isolation, expansion and activation over the past three decades, these have largely been restricted to modelling bone-marrow or blood-derived cells. The in vitro derivation of macrophages from human pluripotent stem cells provides new opportunities to study macrophage biology, including the factors that impact human myeloid development and those that induce macrophage activation. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03014681183008
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http://dx.doi.org/10.1016/j.diff.2018.10.001DOI Listing
October 2018
18 Reads

NR2F1 mediated down-regulation of osteoblast differentiation was rescued by bone morphogenetic protein-2 (BMP-2) in human MSC.

Differentiation 2018 Nov - Dec;104:36-41. Epub 2018 Oct 29.

Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia. Electronic address:

Endochondral ossification is the process by which long bones are formed; the process of long bone formation is regulated by numerous factors such as transcription factors, cytokines, and extracellular matrix molecules. Human hormone Nuclear receptors (hHNR) are a family of ligand-regulated transcription factors that are activated by steroid hormones, such as estrogen and progesterone, and various lipid-soluble signals, including retinoic acid, oxysterols, and thyroid hormone. Whole genome microarray data from our previous study revealed that most hHNR's are up-regulated during osteoblast differentiation in hMSCS. Read More

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http://dx.doi.org/10.1016/j.diff.2018.10.003DOI Listing
October 2018
2 Reads

The renaissance of human skin organ culture: A critical reappraisal.

Differentiation 2018 Nov - Dec;104:22-35. Epub 2018 Oct 16.

Department of Dermatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Human skin organ culture (hSOC) is a simple but highly instructive and clinically relevant skin research method. It has been used for decades to study the development, differentiation, and function as well as the response to wounding or test agents of intact human skin in the presence of its appendages and all resident cell populations. hSOC has also proven useful in toxicological and oncological studies and studies of skin aging (both chronological aging and photoaging), skin energy metabolism, skin immunology, pigmentation biology, and cutaneous (neuro-)endocrinology and neurobiology. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03014681183005
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http://dx.doi.org/10.1016/j.diff.2018.10.002DOI Listing
October 2018
10 Reads

Immunohistochemical expression analysis of the human fetal lower urogenital tract.

Differentiation 2018 Sep - Oct;103:100-119. Epub 2018 Sep 19.

Department of Urology, University of California, San Francisco, San Francisco, CA, United States; Division of Pediatric Urology, University of California San Francisco Benioff Children's Hospital, San Francisco, CA, United States. Electronic address:

We have studied the ontogeny of the developing human male and female urogenital tracts from 9 weeks (indifferent stage) to 16 weeks (advanced sex differentiation) of gestation by immunohistochemistry on mid-sagittal sections. Sixteen human fetal pelvises were serial sectioned in the sagittal plane and stained with antibodies to epithelial, muscle, nerve, proliferation and hormone receptor markers. Key findings are: (1) The corpus cavernosum in males and females extends into the glans penis and clitoris, respectively, during the ambisexual stage (9 weeks) and thus appears to be an androgen-independent event. Read More

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http://dx.doi.org/10.1016/j.diff.2018.09.004DOI Listing
September 2018
7 Reads

Optimal human iPS cell culture method for efficient hepatic differentiation.

Differentiation 2018 Nov - Dec;104:13-21. Epub 2018 Sep 24.

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan; Laboratory of Hepatocyte Regulation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Global Center for Medical Engineering and Informatics, Osaka University, Osaka 565-0871, Japan. Electronic address:

Hepatocyte-like cells differentiated from human iPS cells are expected to be utilized in pharmaceutical research and regenerative medicine. Recently, various culture methods for human iPS cell maintenance have been developed. However, it is not well known whether human iPS cell maintenance method affects hepatic differentiation potency. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03014681183005
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http://dx.doi.org/10.1016/j.diff.2018.09.005DOI Listing
September 2018
3 Reads

Development of human male and female urogenital tracts.

Differentiation 2018 Sep - Oct;103:1-4. Epub 2018 Sep 13.

University of California, San Francisco, Department of Urology, San Francisco, CA 94143, United States.

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http://dx.doi.org/10.1016/j.diff.2018.09.002DOI Listing
September 2018
1 Read

Three-dimensional imaging of the developing human fetal urogenital-genital tract: Indifferent stage to male and female differentiation.

Differentiation 2018 Sep - Oct;103:14-23. Epub 2018 Sep 13.

Department of Urology, University of California, San Francisco, San Francisco, CA, USA; Division of Pediatric Urology, University of California San Francisco Benioff Children's Hospital, 550 16th St, 5th Floor, Mission Hall Pediatric Urology, San Francisco, CA 94158, USA. Electronic address:

Recent studies in our lab have utilized three imaging techniques to visualize the developing human fetal urogenital tract in three dimensions: optical projection tomography, scanning electron microscopy and lightsheet fluorescence microscopy. We have applied these technologies to examine changes in morphology and differential gene expression in developing human external genital specimens from the ambisexual stage (<9 weeks fetal age) to well-differentiated male and female organs (>13 weeks fetal age). This work outlines the history and function of each of these three imaging modalities, our methods to prepare specimens for each and the novel findings we have produced thus far. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03014681183010
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http://dx.doi.org/10.1016/j.diff.2018.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234091PMC
September 2018
4 Reads

Development of the human penis and clitoris.

Differentiation 2018 Sep - Oct;103:74-85. Epub 2018 Aug 23.

UCSF, USA.

The human penis and clitoris develop from the ambisexual genital tubercle. To compare and contrast the development of human penis and clitoris, we used macroscopic photography, optical projection tomography, light sheet microscopy, scanning electron microscopy, histology and immunohistochemistry. The human genital tubercle differentiates into a penis under the influence of androgens forming a tubular urethra that develops by canalization of the urethral plate to form a wide diamond-shaped urethral groove (opening zipper) whose edges (urethral folds) fuse in the midline (closing zipper). Read More

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http://dx.doi.org/10.1016/j.diff.2018.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234061PMC
August 2018
3 Reads

Human glans and preputial development.

Differentiation 2018 Sep - Oct;103:86-99. Epub 2018 Aug 23.

UCSF, USA. Electronic address:

The urethra within the human penile shaft develops via (1) an "Opening Zipper" that facilitates distal canalization of the solid urethral plate to form a wide urethral groove and (2) a "Closing Zipper" that facilitates fusion of the epithelial surfaces of the urethral folds. Herein, we extend our knowledge by describing formation of the human urethra within the glans penis as well as development of the prepuce. Forty-eight normal human fetal penile specimens were examined using scanning electron microscopy and optical projection tomography. Read More

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http://dx.doi.org/10.1016/j.diff.2018.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234068PMC
August 2018
1 Read

Macroscopic whole-mounts of the developing human fetal urogenital-genital tract: Indifferent stage to male and female differentiation.

Differentiation 2018 Sep - Oct;103:5-13. Epub 2018 Aug 30.

Department of Urology, University of California, San Francisco, San Francisco, CA, United States; Division of Pediatric Urology, University of California San Francisco Benioff Children's Hospital, San Francisco, CA, United States. Electronic address:

We present a detailed review of fetal development of the male and female human urogenital tract from 8 to 22 weeks gestation at the macroscopic and morphometric levels. Human fetal specimens were sexed based on macroscopic identification of fetal testes or ovaries, Wolffian or Müllerian structures and the presence of the SRY gene in the specimens at or near the indifferent stage (8-9 weeks). Specimens were photographed using a dissecting microscope with transmitted and reflected light. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03014681183009
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http://dx.doi.org/10.1016/j.diff.2018.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234077PMC
August 2018
2 Reads

Development of the human female reproductive tract.

Differentiation 2018 Sep - Oct;103:46-65. Epub 2018 Sep 6.

Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA 94143, USA.

Development of the human female reproductive tract is reviewed from the ambisexual stage to advanced development of the uterine tube, uterine corpus, uterine cervix and vagina at 22 weeks. Historically this topic has been under-represented in the literature, and for the most part is based upon hematoxylin and eosin stained sections. Recent immunohistochemical studies for PAX2 (reactive with Müllerian epithelium) and FOXA1 (reactive with urogenital sinus epithelium and its known pelvic derivatives) shed light on an age-old debate on the derivation of vaginal epithelium supporting the idea that human vaginal epithelium derives solely from urogenital sinus epithelium. Read More

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http://dx.doi.org/10.1016/j.diff.2018.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234064PMC
September 2018
2 Reads
2 Citations
3.440 Impact Factor

Development of the human bladder and ureterovesical junction.

Differentiation 2018 Sep - Oct;103:66-73. Epub 2018 Aug 28.

Department of Urology, University of California, San Francisco, San Francisco, CA Division of Pediatric Urology, University of California San Francisco Benioff Children's Hospital, San Francisco, CA 94143, United States. Electronic address:

The urinary bladder collects urine from the kidneys and stores it until the appropriate moment for voiding. The trigone and ureterovesical junctions are key to bladder function, by allowing one-way passage of urine into the bladder without obstruction. Embryological development of these structures has been studied in multiple animal models as well as humans. Read More

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http://dx.doi.org/10.1016/j.diff.2018.08.004DOI Listing
August 2018
1 Read

Development of the human prostate.

Differentiation 2018 Sep - Oct;103:24-45. Epub 2018 Sep 4.

Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA 94143, United States.

This paper provides a detailed compilation of human prostatic development that includes human fetal prostatic gross anatomy, histology, and ontogeny of selected epithelial and mesenchymal differentiation markers and signaling molecules throughout the stages of human prostatic development: (a) pre-bud urogenital sinus (UGS), (b) emergence of solid prostatic epithelial buds from urogenital sinus epithelium (UGE), (c) bud elongation and branching, (d) canalization of the solid epithelial cords, (e) differentiation of luminal and basal epithelial cells, and (f) secretory cytodifferentiation. Additionally, we describe the use of xenografts to assess the actions of androgens and estrogens on human fetal prostatic development. In this regard, we report a new model of de novo DHT-induction of prostatic development from xenografts of human fetal female urethras, which emphasizes the utility of the xenograft approach for investigation of initiation of human prostatic development. Read More

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http://dx.doi.org/10.1016/j.diff.2018.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234090PMC
September 2018
1 Read

The role of E2F1-topoIIβ signaling in regulation of cell cycle exit and neuronal differentiation of human SH-SY5Y cells.

Differentiation 2018 Nov - Dec;104:1-12. Epub 2018 Jul 25.

Department of Human Anatomy, Hebei Medical University, Hebei, PR China.

This study aims to test the role of E2F1-topoIIβ signaling in neuronal differentiation of SH-SY5Y cells. With retinoic acid (RA) induction, a high percentage of cells were found to be arrested at the G/G phase, with decreased levels of cyclinD1, CDK4, phosphorylation status of pRb and E2F1, in addition to an elevated level of p27. The cells were shown to differentiate into neuronal phenotypes characterized by highly expressed neuronal markers, MAP2 and enriched topoIIβ, and remarkable neurite outgrowth. Read More

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http://dx.doi.org/10.1016/j.diff.2018.07.002DOI Listing
July 2018
3 Reads

Presenilin gene function and Notch signaling feedback regulation in the developing mouse lens.

Differentiation 2018 Jul - Aug;102:40-52. Epub 2018 Jul 25.

Department of Cell Biology & Human Anatomy; University of California, Davis One Shields Avenue, Davis, CA 95616, USA; Division of Developmental Biology, Cincinnati Childrens Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Electronic address:

Presenilins (Psen1 and Psen2 in mice) are polytopic transmembrane proteins that act in the γ-secretase complex to make intra-membrane cleavages of their substrates, including the well-studied Notch receptors. Such processing releases the Notch intracellular domain, allowing it to physically relocate from the cell membrane to the nucleus where it acts in a transcriptional activating complex to regulate downstream genes in the signal-receiving cell. Previous studies of Notch pathway mutants for Jagged1, Notch2, and Rbpj demonstrated that canonical signaling is a necessary component of normal mouse lens development. Read More

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http://dx.doi.org/10.1016/j.diff.2018.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089524PMC
November 2018
1 Read

Comparison of phenotypes and transcriptomes of mouse skin-derived precursors and dermal mesenchymal stem cells.

Differentiation 2018 Jul - Aug;102:30-39. Epub 2018 Jul 20.

Department of Dermatology and Venerology, Huaxi Hospital, Chengdu, Sichuan Province, PR China. Electronic address:

Both skin-derived precursors (SKPs) and dermal mesenchymal stem cells (dMSCs) are promising candidates for cellular therapy and regenerative medicine. To date the comparison of phenotypes and transcriptomes of mouse SKPs (mSKPs) and dMSCs has never been reported. Here we characterized and compared the biological properties and transcriptomes of mSKP and dMSCs from the same mouse dermis sample. Read More

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http://dx.doi.org/10.1016/j.diff.2018.07.001DOI Listing
November 2018
4 Reads
3.440 Impact Factor

Telomere regulation.

Authors:
Brian Luke

Differentiation 2018 Jul - Aug;102:27-29. Epub 2018 Jun 30.

Institute of Neurobiology and Developmental Biology, Johannes Gutenberg University, IMB-Mainz, Ackermannweg 4, 55128 Mainz, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.diff.2018.06.002DOI Listing
November 2018
1 Read

Interstitial telomeric loops and implications of the interaction between TRF2 and lamin A/C.

Differentiation 2018 Jul - Aug;102:19-26. Epub 2018 Jun 18.

Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address:

The protein-DNA complexes that compose the end of mammalian chromosomes-telomeres-serve to stabilize linear genomic DNA and are involved in cellular and organismal aging. One mechanism that protects telomeres from premature degradation is the formation of structures called t-loops, in which the single-stranded 3' overhang present at the terminal end of telomeres loops back and invades medial double-stranded telomeric DNA. We identified looped structures formed between terminal chromosome ends and interstitial telomeric sequences (ITSs), which are found throughout the human genome, that we have termed interstitial telomeric loops (ITLs). Read More

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http://dx.doi.org/10.1016/j.diff.2018.06.001DOI Listing
November 2018
1 Read

Contrasting mechanisms of penile urethral formation in mouse and human.

Differentiation 2018 May - Jun;101:46-64. Epub 2018 May 17.

Department of Urology, University of California, San Francisco, CA, United States. Electronic address:

This paper addresses the developmental mechanisms of formation of the mouse and human penile urethra and the possibility that two disparate mechanisms are at play. It has been suggested that the entire penile urethra of the mouse forms via direct canalization of the endodermal urethral plate. While this mechanism surely accounts for development of the proximal portion of the mouse penile urethra, we suggest that the distal portion of the mouse penile urethra forms via a series of epithelial fusion events. Read More

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http://dx.doi.org/10.1016/j.diff.2018.05.001DOI Listing
November 2018
18 Reads

Glucocorticoid-induced pancreatic-hepatic trans-differentiation in a human cell line in vitro.

Differentiation 2018 Jul - Aug;102:10-18. Epub 2018 May 22.

Institute of Cellular Medicine, Newcastle University, Level 4 William Leech Building, Medical School, Framlington Place, Newcastle Upon Tyne NE2 4HH, UK. Electronic address:

The rodent pancreatic AR42J-B13 (B-13) cell line differentiates into non-replicative hepatocyte-like cells in response to glucocorticoid mediated via the glucocorticoid receptor (GR). The aims of this study were to identify a human cell line that responds similarly and investigate the mechanisms underpinning any alteration in differentiation. Exposing the human pancreatic adenocarcinoma (HPAC) cell line to 1-10 µM concentrations of dexamethasone (DEX) resulted an inhibition of proliferation, suppressed carcinoembryonic antigen expression, limited expression of pancreatic acinar and hepatic gene expression and significant induction of the constitutively-expressed hepatic CYP3A5 mRNA transcript. Read More

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http://dx.doi.org/10.1016/j.diff.2018.05.003DOI Listing
November 2018
2 Reads

Epha2 and Efna5 participate in lens cell pattern-formation.

Differentiation 2018 Jul - Aug;102:1-9. Epub 2018 May 17.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

Ephrin type-A receptor 2 (EPHA2) and one of its ligands, ephrin-A5 (EFNA5), have been associated with loss of eye lens transparency, or cataract, - an important cause of visual impairment. Here we show that mice functionally lacking EPHA2 (Epha2-null), EFNA5 (Efna5-null), or both receptor and ligand (Epha2/Efna5-null) consistently develop mostly transparent lenses with an internal refractive disturbance and a grossly disturbed cellular architecture. In situ hybridization localized Epha2 and Efna5 transcripts to lens epithelial cells and nascent fiber cells at the lens equator. Read More

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http://dx.doi.org/10.1016/j.diff.2018.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287607PMC
November 2018
2 Reads

Tissue interactions and estrogenic response during human female fetal reproductive tract development.

Differentiation 2018 May - Jun;101:39-45. Epub 2018 Apr 18.

Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA 94143, United States.

The role of tissue interactions was explored to determine whether epithelial differentiation within the developing human reproductive tract is induced and specified by mesenchyme in tissue recombinants composed of mouse vaginal mesenchyme + human uterine tubal epithelium (mVgM+hTubE). The tissue recombinants were grown in DES-treated ovariectomized athymic mice. After 2-4 weeks of in vivo growth, several vaginal specific features were expressed in the human tubal epithelium. Read More

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http://dx.doi.org/10.1016/j.diff.2018.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993605PMC
November 2018
1 Read
3.440 Impact Factor

Development of urogenital system in the Spix cavy: A model for studies on sexual differentiation.

Differentiation 2018 May - Jun;101:25-38. Epub 2018 Apr 13.

Department of Surgery, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87 ZC, 05508-270 São Paulo-SP, Brazil. Electronic address:

This study documented, for the first time, the morphological patterns of differentiation of male and female genital organs of Spix cavy (Galea spixii) using histological and ultrastructural analyses, with immuno-localization of steroidogenic enzymes, cytochromes P450 aromatase (P450arom) and 17α-hydroxylase/17, 20-lyase (P450c17), involved in the synthesis of estrogens and androgens respectively throughout fetal sexual development. Undifferentiated gonads of Spix cavy develop into ovaries in females after 25 days of gestation (DG), exhibiting P450arom immunoreactivity. After 25 DG, paramesonephric ducts develop and form oviducts, uterine horns and cranial portion of the vagina. Read More

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http://dx.doi.org/10.1016/j.diff.2018.04.001DOI Listing
November 2018
4 Reads

Differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules.

Differentiation 2018 May - Jun;101:16-24. Epub 2018 Mar 27.

Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, FL 33136, United States.

A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Read More

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http://dx.doi.org/10.1016/j.diff.2018.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055513PMC
November 2018
16 Reads

Stem cells from apical papilla promote differentiation of human pluripotent stem cells towards retinal cells.

Differentiation 2018 May - Jun;101:8-15. Epub 2018 Mar 2.

Department of Developmental Biology, University of Science and Culture, Tehran, Iran; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic address:

Recently, we have found that human stem cells from apical papilla (SCAP) show a stromal cell-derived inducing activity (SDIA). To examine SDIA competence for retinal cells differentiation, we co-cultured SCAP with human pluripotent stem cells (hPSCs). In comparison with Matrigel-cultured hPSCs, SCAP significantly induces hPSCs to differentiate into rostral neural cells as demonstrated by upregulation of OTX2 and PAX6 and down-regulation of EN1, HOXB4 and HOXC8. Read More

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http://dx.doi.org/10.1016/j.diff.2018.02.003DOI Listing
November 2018
6 Reads

Vitamin C-linker-conjugated tripeptide AHK stimulates BMP-2-induced osteogenic differentiation of mouse myoblast C2C12 cells.

Differentiation 2018 May - Jun;101:1-7. Epub 2018 Mar 15.

Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 34824, Republic of Korea. Electronic address:

Vitamin C-linker-conjugated Ala-His-Lys tripeptide (Vit C-AHK) is a derivative of Vitamin C-conjugated tripeptides, which were originally developed as a component of a product for collagen synthesis enhancement or human dermal fibroblast growth. Here, we investigated the effect of Vit C-AHK on bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Vit C-AHK enhanced proliferation of C2C12 cells and induction of BMP-2-induced alkaline phosphatase, a typical marker of osteoblast differentiation. Read More

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http://dx.doi.org/10.1016/j.diff.2018.03.001DOI Listing
November 2018
9 Reads
3.440 Impact Factor

Transcriptome analysis identifies genes involved in sex determination and development of Xenopus laevis gonads.

Differentiation 2018 Mar - Apr;100:46-56. Epub 2018 Mar 2.

Univ Rennes, UMR 6290, Institute of Genetics and Development of Rennes, Cell Cycle Group, Faculty of Medicine, F-35000 Rennes, France; Laboratory of Regenerative Medicine and Cell Biology, Military Institute of Hygiene and Epidemiology (WIHE), Warsaw, Poland.

Development of the gonads is a complex process, which starts with a period of undifferentiated, bipotential gonads. During this period the expression of sex-determining genes is initiated. Sex determination is a process triggering differentiation of the gonads into the testis or ovary. Read More

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http://dx.doi.org/10.1016/j.diff.2018.02.004DOI Listing
November 2018
8 Reads

Increased TERRA levels and RNase H sensitivity are conserved hallmarks of post-senescent survivors in budding yeast.

Differentiation 2018 Mar - Apr;100:37-45. Epub 2018 Feb 16.

Institute of Neurobiology and Developmental Biology, JGU Mainz, Ackermannweg 4, 55128 Mainz, Germany; Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz, Germany. Electronic address:

Cancer cells activate telomere maintenance mechanisms (TMMs) to bypass replicative senescence and achieve immortality by either upregulating telomerase or promoting homology-directed repair (HDR) at chromosome ends to maintain telomere length, the latter being referred to as ALT (Alternative Lengthening of Telomeres). In yeast telomerase mutants, the HDR-based repair of telomeres leads to the generation of 'survivors' that escape senescence and divide indefinitely. So far, yeast has proven to provide an accurate model to study the generation and maintenance of telomeres via HDR. Read More

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http://dx.doi.org/10.1016/j.diff.2018.02.002DOI Listing
November 2018
10 Reads

Short telomeres - A hallmark of heritable cardiomyopathies.

Differentiation 2018 Mar - Apr;100:31-36. Epub 2018 Feb 9.

Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA. Electronic address:

Cardiovascular diseases are the leading cause of death worldwide and the incidence increases with age. Genetic testing has taught us much about the pathogenic pathways that drive heritable cardiomyopathies. Here we discuss an unexpected link between shortened telomeres, a molecular marker of aging, and genetic cardiomyopathy. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S03014681183000
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http://dx.doi.org/10.1016/j.diff.2018.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889329PMC
November 2018
6 Reads

Telomeres and telomerase in heart regeneration.

Differentiation 2018 Mar - Apr;100:26-30. Epub 2018 Feb 3.

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernandez Almagro 3, Madrid E-28029, Spain. Electronic address:

Although recent advances have overturned the old view of the human heart as an inert postmitotic organ, it is clear that the adult heart´s capacity to regenerate after an ischemic episode is very limited. Unlike humans, zebrafish and other lower vertebrates vigorously regenerate damaged myocardium after cardiac injury. Understanding how the zebrafish is able to conserve life-long cardiac regeneration capacity while mammals lose it soon after birth is crucial for the development of new treatments for myocardial infarction. Read More

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http://dx.doi.org/10.1016/j.diff.2018.01.003DOI Listing
November 2018
4 Reads

How stem cells keep telomeres in check.

Differentiation 2018 Mar - Apr;100:21-25. Epub 2018 Feb 2.

Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address:

In multicellular organisms, regulation of telomere length in pluripotent stem cells is critical to ensure organism development and survival. Telomeres consist of repetitive DNA that are progressively lost with each cellular division. When telomeres become critically short, they activate a DNA damage response that results in cell cycle arrest. Read More

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http://dx.doi.org/10.1016/j.diff.2018.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889314PMC
November 2018
5 Reads

Stretching, scrambling, piercing and entangling: Challenges for telomeres in mitotic and meiotic chromosome segregation.

Differentiation 2018 Mar - Apr;100:12-20. Epub 2018 Jan 31.

Telomere Biology Section, LBMB, NCI, NIH, Building 37, Room 6050, Bethesda MD 20892, USA. Electronic address:

The consequences of telomere loss or dysfunction become most prominent when cells enter the nuclear division stage of the cell cycle. At this climactic stage when chromosome segregation occurs, telomere fusions or entanglements can lead to chromosome breakage, wreaking havoc on genome stability. Here we review recent progress in understanding the mechanisms of detangling and breaking telomere associations at mitosis, as well as the unique ways in which telomeres are processed to allow regulated sister telomere separation. Read More

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http://dx.doi.org/10.1016/j.diff.2018.01.002DOI Listing
November 2018
2 Reads

Dysfunctional telomeres and hematological disorders.

Differentiation 2018 Mar - Apr;100:1-11. Epub 2018 Jan 4.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:

Telomere biology disorders, which are characterized by telomerase activity haploinsufficiency and accelerated telomere shortening, most commonly manifest as degenerative diseases. Tissues with high rates of cell turnover, such as those in the hematopoietic system, are particularly vulnerable to defects in telomere maintenance genes that eventually culminate in bone marrow (BM) failure syndromes, in which the BM cannot produce sufficient new blood cells. Here, we review how telomere defects induce degenerative phenotypes across multiple organs, with particular focus on how they impact the hematopoietic stem and progenitor compartment and affect hematopoietic stem cell (HSC) self-renewal and differentiation. Read More

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http://dx.doi.org/10.1016/j.diff.2018.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889327PMC
November 2018
7 Reads

The ubiquitin ligase ITCH coordinates small intestinal epithelial homeostasis by modulating cell proliferation, differentiation, and migration.

Differentiation 2018 Jan - Feb;99:51-61. Epub 2017 Dec 15.

Department of Biological Sciences, University of South Carolina, 715 Sumter St., Columbia, SC 29208, USA. Electronic address:

Maintenance of the intestinal mucosa is driven by local signals that coordinate epithelial proliferation, differentiation, and turnover in order to separate antigenic luminal contents from the host's immune system. Breaches in this barrier promote gastrointestinal pathologies ranging from inflammatory bowel disease to cancer. The ubiquitin ligase ITCH is known to regulate immune responses, and loss of function of ITCH has been associated with gastrointestinal inflammatory disorders, particularly in the colon. Read More

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http://dx.doi.org/10.1016/j.diff.2017.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826883PMC
November 2018
6 Reads

Telomeres in cancer.

Differentiation 2018 Jan - Feb;99:41-50. Epub 2017 Dec 21.

Research Group on Stem Cell Aging, Leibniz Institute on Aging, Fritz Lipmann Institute (FLI), Beutenbergstr. 11, 07745 Jena, Germany. Electronic address:

Telomere shortening as a consequence of cell divisions during aging and chronic diseases associates with an increased cancer risk. Experimental data revealed that telomere shortening results in telomere dysfunction, which in turn affects tumorigenesis in two ways. First, telomere dysfunction suppresses tumor progression by the activation of DNA damage checkpoints, which induce cell cycle arrest (senescence) or apoptosis, as well as by inducing metabolic compromise and activation of immune responses directed against senescent cells. Read More

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http://dx.doi.org/10.1016/j.diff.2017.12.004DOI Listing
November 2018
3 Reads

The role of gastrulation brain homeobox 2 (gbx2) in the development of the ventral telencephalon in zebrafish embryos.

Differentiation 2018 Jan - Feb;99:28-40. Epub 2017 Dec 21.

Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama City, Saitama 338-8570, Japan; Saitama University Brain Science Institute, Shimo-Okubo, Sakura-ku, Saitama City, Saitama 338-8570, Japan. Electronic address:

During vertebrate brain development, the gastrulation brain homeobox 2 gene (gbx2) is expressed in the forebrain, but its precise roles are still unknown. In this study, we addressed this issue in zebrafish (Danio rerio) first by carefully examining gbx2 expression in the developing forebrain. We showed that gbx2 was expressed in the telencephalon during late somitogenesis, from 18h post-fertilization (hpf) to 24 hpf, and in the thalamic primordium after 26 hpf. Read More

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http://dx.doi.org/10.1016/j.diff.2017.12.005DOI Listing
November 2018
4 Reads

Impact of oxidative stress on telomere biology.

Differentiation 2018 Jan - Feb;99:21-27. Epub 2017 Dec 14.

Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address:

Telomere integrity is essential for genome stability and it regulates cell proliferation and tissue renewal. Several lines of evidence indicate that telomeres are particularly sensitive to oxidative damage. Moreover, recent studies demonstrate striking inhibitory effects of oxidative damage on telomerase activity. Read More

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http://dx.doi.org/10.1016/j.diff.2017.12.002DOI Listing
November 2018
5 Reads

Mechanisms of epithelial thickening due to IL-1 signalling blockade and TNF-α administration differ during wound repair and regeneration.

Differentiation 2018 Jan - Feb;99:10-20. Epub 2017 Dec 12.

Laboratory of Connective Tissue, Centro Nacional de Investigación y Atención de Quemados, Instituto Nacional de Rehabilitación Luís Guillermo Ibarra Ibarra, México-Xochimilco No. 289, Col. Arenal de Guadalupe, Del. Tlalpan, C.P. 14389 Mexico City, Mexico. Electronic address:

IL-1 and TNF-α are always present during wound repair, but their pleiotropic and synergistic effects are incompletely understood. In this work, we evaluated the role of IL-1 in wound repair, and examined whether TNF-α administration impaired scarless wound repair. First, we characterised wound repair in outbred CD-1 mice according to age and sex in an ear punch wound model. Read More

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http://dx.doi.org/10.1016/j.diff.2017.12.001DOI Listing
November 2018
7 Reads

Directed differentiation of periocular mesenchyme from human embryonic stem cells.

Differentiation 2018 Jan - Feb;99:62-69. Epub 2017 Nov 16.

Singapore National Eye Centre, 11 Third Hospital Ave, #08-00, Singapore 168751, Singapore; Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower Level 12, Singapore 169856, Singapore.

Corneal tissue is the most transplanted of all body tissues. Currently, cadaveric donor tissues are used for transplantation. However, a global shortage of transplant grade material has prompted development of alternative, cell-based therapies for corneal diseases. Read More

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http://dx.doi.org/10.1016/j.diff.2017.11.003DOI Listing
November 2018
5 Reads

Use of immune-deficient hosts to study human development and pathogenesis.

Authors:
Gerald R Cunha

Differentiation 2017 Nov - Dec;98:A1-A3

Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA 94143, United States. Electronic address:

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http://dx.doi.org/10.1016/j.diff.2017.11.006DOI Listing
January 2019
8 Reads

Long-range telomere regulation of gene expression: Telomere looping and telomere position effect over long distances (TPE-OLD).

Differentiation 2018 Jan - Feb;99:1-9. Epub 2017 Nov 22.

Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address:

The human cellular reverse transcriptase, telomerase, is very tightly regulated in large long-lived species. Telomerase is expressed during early human fetal development, is turned off in most adult tissues, and then becomes reactivated in almost all human cancers. However, the exact mechanism regulating these switches in expression are not known. Read More

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http://dx.doi.org/10.1016/j.diff.2017.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826875PMC
November 2018
6 Reads