6,373 results match your criteria terminally differentiated


Meflin defines mesenchymal stem cells and/or their early progenitors with multilineage differentiation capacity.

Genes Cells 2021 May 7. Epub 2021 May 7.

Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.

Mesenchymal stem cells (MSCs) are the likely precursors of multiple lines of mesenchymal cells. The existence of bona fide MSCs with self-renewal capacity and differentiation potential into all mesenchymal lineages, however, has been unclear because of the lack of MSC-specific marker(s) that are not expressed by the terminally differentiated progeny. Meflin, a glycosylphosphatidylinositol-anchored protein, is an MSC marker candidate that is specifically expressed in rare stromal cells in all tissues. Read More

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Twenty-five years after Dolly - How far have we come?

Reproduction 2021 May 1. Epub 2021 May 1.

A Schnieke, Department of Animal Sciences, Technical University of Munich School of Life Sciences Weihenstephan, Freising, Germany.

For more than a century the scientific consensus stated that a nucleus from a terminally differentiated cell would not be able to control the development of offspring. This theory was refuted by the birth of Dolly, the first animal generated by nuclear transfer using an adult somatic cell as nuclear donor. Following this paradigm shift, a wide variety of animals has been cloned using somatic cell nuclear transfer. Read More

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Derivation of Multipotent Neural Progenitors from Human Embryonic Stem Cells for Cell Therapy and Biomedical Applications.

Methods Mol Biol 2021 May 5. Epub 2021 May 5.

Jeffrey Cheah Biomedical Centre, Department of Surgery, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.

Long-term neuroepithelial-like stem cells (lt-NES) derived from human embryonic stem cells are a stable self-renewing progenitor population with high neurogenic potential and phenotypic plasticity. Lt-NES are amenable to regional patterning toward neurons and glia subtypes and thus represent a valuable source of cells for many biomedical applications. For use in regenerative medicine and cell therapy, lt-NES and their progeny require derivation with high-quality culture conditions suitable for clinical use. Read More

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Transcriptional firing represses bactericidal activity in cystic fibrosis airway neutrophils.

Cell Rep Med 2021 Apr 8;2(4):100239. Epub 2021 Apr 8.

Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.

Neutrophils are often considered terminally differentiated and poised for bacterial killing. In chronic diseases such as cystic fibrosis (CF), an unexplained paradox pits massive neutrophil presence against prolonged bacterial infections. Here, we show that neutrophils recruited to CF airways and in an transmigration model display rapid and broad transcriptional firing, leading to an upregulation of anabolic genes and a downregulation of antimicrobial genes. Read More

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Single-keratinocyte transcriptomic analyses identify different clonal types and proliferative potential mediated by FOXM1 in human epidermal stem cells.

Nat Commun 2021 05 4;12(1):2505. Epub 2021 May 4.

Centre for Regenerative Medicine "Stefano Ferrari", University of Modena and Reggio Emilia, Modena, Italy.

Autologous epidermal cultures restore a functional epidermis on burned patients. Transgenic epidermal grafts do so also in genetic skin diseases such as Junctional Epidermolysis Bullosa. Clinical success strictly requires an adequate number of epidermal stem cells, detected as holoclone-forming cells, which can be only partially distinguished from the other clonogenic keratinocytes and cannot be prospectively isolated. Read More

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DNA damage and repair in differentiation of stem cells and cells of connective cell lineages: A trigger or a complication?

Eur J Histochem 2021 May 3;65(2). Epub 2021 May 3.

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The review summarizes literature data on the role of DNA breaks and DNA repair in differentiation of pluripotent stem cells (PSC) and connective cell lineages. PSC, including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC), are rapidly dividing cells with highly active DNA damage response (DDR) mechanisms to ensure the stability and integrity of the DNA. In PSCs, the most common DDR mechanism is error-free homologous recombination (HR) that is primarily active during S phase of the cell cycle, whereas in quiescent, slow-dividing or non-dividing tissue progenitors and terminally differentiated cells, error-prone non-homologous end joining (NHEJ) mechanism of the double-strand break (DSB) repair is dominating. Read More

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T cell plasticity in renal autoimmune disease.

Cell Tissue Res 2021 May 3. Epub 2021 May 3.

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

The presence of immune cells is a morphological hallmark of rapidly progressive glomerulonephritis, a disease group that includes anti-glomerular basement membrane glomerulonephritis, lupus nephritis, and anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. The cellular infiltrates include cells from both the innate and the adaptive immune responses. The latter includes CD4 and CD8 T cells. Read More

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Effects of two potential probiotic Lactobacillus bacteria on adipogenesis in vitro.

Life Sci 2021 Apr 28;278:119538. Epub 2021 Apr 28.

School of Biological Sciences, National Institute of Science Education and Research (NISER), P.O. - Bhimpur-Padanpur, Jatni - 752050, Dist.-Khurda, Odisha, India; Homi Bhabha National Institute (HBNI), Training School Complex, Anushaktinagar, Mumbai 400 094, India. Electronic address:

Aims: Overweight is a major global health problem. Various methodologies to get rid of the extra fat are available, but usually, those are associated with adverse side effects. Probiotics, on the contrary, seem to have the potential to help reduce fat accumulation without much apparent adversity. Read More

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Genomic Spectrum and Phenotypic Heterogeneity of Human IL-21 Receptor Deficiency.

J Clin Immunol 2021 Apr 30. Epub 2021 Apr 30.

Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.

Biallelic inactivating mutations in IL21R causes a combined immunodeficiency that is often complicated by cryptosporidium infections. While eight IL-21R-deficient patients have been reported previously, the natural course, immune characteristics of disease, and response to hematopoietic stem cell transplantation (HSCT) remain to be comprehensively examined. In our study, we have collected clinical histories of 13 patients with IL-21R deficiency from eight families across seven centers worldwide, including five novel patients identified by exome or NGS panel sequencing. Read More

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Heterochromatin and Polycomb as regulators of haematopoiesis.

Biochem Soc Trans 2021 Apr 30. Epub 2021 Apr 30.

The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria3052, Australia.

Haematopoiesis is the process by which multipotent haematopoietic stem cells are transformed into each and every type of terminally differentiated blood cell. Epigenetic silencing is critical for this process by regulating the transcription of cell-cycle genes critical for self-renewal and differentiation, as well as restricting alternative fate genes to allow lineage commitment and appropriate differentiation. There are two distinct forms of transcriptionally repressed chromatin: H3K9me3-marked heterochromatin and H3K27me3/H2AK119ub1-marked Polycomb (often referred to as facultative heterochromatin). Read More

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A novel antibody targeting TIM-3 resulting in receptor internalization for cancer immunotherapy.

Antib Ther 2020 Dec 9;3(4):227-236. Epub 2020 Nov 9.

Innovent Biologics (Suzhou) Co., Ltd., 168 Dongping Street, Suzhou Industrial Park, Suzhou 215123, Jiangsu, China.

Background: Strategies to reinvigorate exhausted T cells have achieved great efficacy in certain subpopulations of tumor patients. Blocking the antibodies that target programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 induces durable responses in Hodgkin's lymphoma, melanoma, renal and lung cancers. T cell immunoglobulin mucin-3 (TIM-3) is another well-defined inhibitory receptor that is expressed in terminally differentiated Th1/Tc1 cells, which produces interferon gamma and cytotoxic molecules. Read More

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December 2020

The Presence of a Marked Imbalance Between Regulatory T Cells and Effector T Cells Reveals That Tolerance Mechanisms Could Be Compromised in Heart Transplant Children.

Transplant Direct 2021 May 23;7(5):e693. Epub 2021 Apr 23.

Laboratory of Immune-regulation, Immunology Department, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain.

Regulatory T cells (Treg) are crucial for the induction and maintenance of graft tolerance. In pediatric heart transplant procedures, the thymus is routinely excised, removing the primary source of T-cell replenishment. Consequently, thymectomy joined to the effects of immunosuppression on the T-cell compartment may have a detrimental impact on Treg values, compromising the intrinsic tolerance mechanisms and the protective role of Treg preventing graft rejection in heart transplant children. Read More

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Increased Osteocyte Lacunae Density in the Hypermineralized Bone Matrix of Children with Osteogenesis Imperfecta Type I.

Int J Mol Sci 2021 Apr 26;22(9). Epub 2021 Apr 26.

1st Medical Department, Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, Hanusch Hospital, 1140 Vienna, Austria.

Osteocytes are terminally differentiated osteoblasts embedded within the bone matrix and key orchestrators of bone metabolism. However, they are generally not characterized by conventional bone histomorphometry because of their location and the limited resolution of light microscopy. OI is characterized by disturbed bone homeostasis, matrix abnormalities and elevated bone matrix mineralization density. Read More

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NKL-Code in Normal and Aberrant Hematopoiesis.

Authors:
Stefan Nagel

Cancers (Basel) 2021 Apr 19;13(8). Epub 2021 Apr 19.

Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ, German Collection of Microorganisms and Cell Cultures, Inhoffenstr. 7B, 38124 Braunschweig, Germany.

We have recently described physiological expression patterns of NKL homeobox genes in early hematopoiesis and in subsequent lymphopoiesis and myelopoiesis, including terminally differentiated blood cells. We thereby systematized differential expression patterns of eleven such genes which form the so-called NKL-code. Due to the developmental impact of NKL homeobox genes, these data suggest a key role for their activity in normal hematopoietic differentiation processes. Read More

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Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7-related osteopetrosis.

J Bone Miner Res 2021 Apr 27. Epub 2021 Apr 27.

BIH Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt - Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.

Human induced pluripotent stem cells (hiPSCs) hold great potential for modelling human diseases and the development of innovative therapeutic approaches. Here, we report on a novel, simplified differentiation method for forming functional osteoclasts from hiPSCs. The three-step protocol starts with embryoid body formation, followed by hematopoietic specification, and finally osteoclast differentiation. Read More

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Analysis of peripheral inflammatory T cell subsets and their effector function in patients with Birdshot Retinochoroiditis.

Sci Rep 2021 Apr 21;11(1):8604. Epub 2021 Apr 21.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.

Birdshot Retinochoroiditis (BSRC) is a progressive non-infectious intraocular inflammation that affects choroid and retina. Inflammatory processes have adverse effects on vision by affecting photoreceptor-bearing cells that do not regenerate. This study aimed at characterizing inflammatory CD4 and CD8 T cell subsets in the peripheral blood of active and inactive BSRCs. Read More

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Genomics-Guided Drawing of Molecular and Pathophysiological Components of Malignant Regulatory Signatures Reveals a Pivotal Role in Human Diseases of Stem Cell-Associated Retroviral Sequences and Functionally-Active hESC Enhancers.

Front Oncol 2021 31;11:638363. Epub 2021 Mar 31.

Institute of Engineering in Medicine, University of California, San Diego, CA, United States.

Repetitive DNA sequences (repeats) colonized two-third of human genome and a majority of repeats comprised of transposable genetic elements (TE). Evolutionary distinct categories of TE represent nucleic acid sequences that are repeatedly copied from and pasted into chromosomes at multiple genomic locations and acquired a multitude of regulatory functions. Here, genomics-guided maps of stemness regulatory signatures were drawn to dissect the contribution of TE to clinical manifestations of malignant phenotypes of human cancers. Read More

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Unraveling the Big Sleep: Molecular Aspects of Stem Cell Dormancy and Hibernation.

Front Physiol 2021 1;12:624950. Epub 2021 Apr 1.

Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Tissue-resident stem cells may enter a dormant state, also known as quiescence, which allows them to withstand metabolic stress and unfavorable conditions. Similarly, hibernating mammals can also enter a state of dormancy used to evade hostile circumstances, such as food shortage and low ambient temperatures. In hibernation, the dormant state of the individual and its cells is commonly known as torpor, and is characterized by metabolic suppression in individual cells. Read More

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Challenges in the Diagnosis of Pituitary Neuroendocrine Tumors.

Authors:
Sylvia L Asa

Endocr Pathol 2021 Apr 17. Epub 2021 Apr 17.

Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, 44106, USA.

Detailed analysis of cytodifferentiation and hormone production has classified pituitary neuroendocrine tumors (PitNETs) in a formal system that reflects the lineage differentiation of nontumorous adenohypophysial cells as well as subtypes of tumors that have predictive value. In addition, tumors composed of cells that lack terminal differentiation are well characterized. To comply with the proposal to create an overarching classification of neuroendocrine neoplasia, these tumors are now called PitNETs rather than adenomas. Read More

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Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis.

Cell Immunol 2021 Jun 8;364:104359. Epub 2021 Apr 8.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address:

Conventional anti-tuberculosis (TB) therapies comprise lengthy antibiotic treatment regimens, exacerbated by multi-drug resistant and extensively drug resistant mycobacterial strains. We assessed the ability of all-trans retinoic acid (ATRA), as repurposed compound serving as host-directed therapy (HDT), to counteract the suppressive effects of myeloid-derived suppressor cells (MDSCs) obtained from active TB cases (untreated or during week one of treatment) on T-cell responsiveness. We show for the first time that MDSCs suppress non-specific T-cell activation and production of interleukin (IL)-2, IL-4, IL-13 and GM-CSF via contact-dependent mechanisms. Read More

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The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude.

J Exp Med 2021 Jun;218(6)

Department of Pathology, Committees on Immunology and Cancer Biology, The University of Chicago, Chicago, IL.

Gaining a mechanistic understanding of the expansion and maturation program of natural killer (NK) cells will provide opportunities for harnessing their inflammation-inducing and oncolytic capacity for therapeutic purposes. Here, we demonstrated that ID2, a transcriptional regulatory protein constitutively expressed in NK cells, supports NK cell effector maturation by controlling the amplitude and temporal dynamics of the transcription factor TCF1. TCF1 promotes immature NK cell expansion and restrains differentiation. Read More

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Characterization of CD31 expression in CD4+ and CD8+T cell subpopulations in chronic untreated HIV infection.

Immunol Lett 2021 Apr 11. Epub 2021 Apr 11.

Instituto Nacional de Enfermedades Respiratorias, Centro de Investigación en Enfermedades Infecciosas, México City, Mexico.

Background: The platelet endothelial cell adhesion molecule-1 (PECAM-1) or CD31 has been involved in regulation of T-cell tolerance, activation, survival and homing in mice cells. However, there is limited knowledge about the expression pattern and role of this molecule in human T cells, particularly in conditions of chronic immune activation.

Objectives: We explored CD31 expression in T cell differentiation subsets of individuals with untreated HIV infection and in non-HIV-infected controls. Read More

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Telomere erosion in human pluripotent stem cells leads to ATR-mediated mitotic catastrophe.

J Cell Biol 2021 Jun;220(6)

Department of Medicine, Washington University in St. Louis, St. Louis, MO.

It is well established that short telomeres activate an ATM-driven DNA damage response that leads to senescence in terminally differentiated cells. However, technical limitations have hampered our understanding of how telomere shortening is signaled in human stem cells. Here, we show that telomere attrition induces ssDNA accumulation (G-strand) at telomeres in human pluripotent stem cells (hPSCs), but not in their differentiated progeny. Read More

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[Relationship between neutrophil phenotypic and functional heterogeneity and diseases].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Mar;33(3):360-363

Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin 300100, China. Corresponding author: Wang Ximo, Email:

Neutrophils are the most abundant circulating leukocyte type in humans and comprise the host's first line of cellular defense against foreign pathogens invasion. On the other hand, neutrophils are the main mediators of tissue damage induced by acute and chronic inflammation. They were once considered to be short-lived, low transcriptional activity, and terminally differentiated homogeneous leucocytes that failed to return to circulation from tissue. Read More

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The Hsp70 chaperone system: distinct roles in erythrocyte formation and maintenance.

Haematologica 2021 Apr 8. Epub 2021 Apr 8.

Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria.

Erythropoiesis is a tightly regulated cell differentiation process in which specialized oxygen- and carbon dioxide-carrying red blood cells are generated in vertebrates. Extensive reorganization and depletion of the erythroblast proteome leading to the deterioration of general cellular protein quality control pathways and rapid hemoglobin biogenesis rates could generate misfolded/aggregated proteins and trigger proteotoxic stresses during erythropoiesis. Such cytotoxic conditions could prevent proper cell differentiation resulting in premature apoptosis of erythroblasts (ineffective erythropoiesis). Read More

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Method for selective ablation of undifferentiated human pluripotent stem cell populations for cell-based therapies.

JCI Insight 2021 Apr 8;6(7). Epub 2021 Apr 8.

Stanford Cardiovascular Institute.

Human pluripotent stem cells (PSCs), which are composed of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), provide an opportunity to advance cardiac cell therapy-based clinical trials. However, an important hurdle that must be overcome is the risk of teratoma formation after cell transplantation due to the proliferative capacity of residual undifferentiated PSCs in differentiation batches. To tackle this problem, we propose the use of a minimal noncardiotoxic doxorubicin dose as a purifying agent to selectively target rapidly proliferating stem cells for cell death, which will provide a purer population of terminally differentiated cardiomyocytes before cell transplantation. Read More

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Uncovering cellular networks in branching morphogenesis using single-cell transcriptomics.

Curr Top Dev Biol 2021 5;143:239-280. Epub 2020 Nov 5.

Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, United States; Department of Molecular Biology, Princeton University, Princeton, NJ, United States. Electronic address:

Single-cell RNA-sequencing (scRNA-seq) and related technologies to identify cell types and measure gene expression in space, in time, and within lineages have multiplied rapidly in recent years. As these techniques proliferate, we are seeing an increase in their application to the study of developing tissues. Here, we focus on single-cell investigations of branching morphogenesis. Read More

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November 2020

Harnessing the IL-21-BATF Pathway in the CD8 T Cell Anti-Tumor Response.

Cancers (Basel) 2021 Mar 12;13(6). Epub 2021 Mar 12.

Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53226, USA.

In cancer, CD8 T cells enter a dysfunctional state which prevents them from effectively targeting and killing tumor cells. Tumor-infiltrating CD8 T cells consist of a heterogeneous population of memory-like progenitor, effector, and terminally exhausted cells that exhibit differing functional and self-renewal capacities. Our recently published work has shown that interleukin (IL)-21-producing CD4 T cells help to generate effector CD8 T cells within the tumor, which results in enhanced tumor control. Read More

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Podocyte Autophagy in Homeostasis and Disease.

J Clin Med 2021 Mar 12;10(6). Epub 2021 Mar 12.

Division of Nephrology, Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Autophagy is a protective mechanism that removes dysfunctional components and provides nutrition for cells. Podocytes are terminally differentiated specialized epithelial cells that wrap around the capillaries of the glomerular filtration barrier and show high autophagy level at the baseline. Here, we provide an overview of cellular autophagy and its regulation in homeostasis with specific reference to podocytes. Read More

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Immunological Prognostic Factors in Multiple Myeloma.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland.

Multiple myeloma (MM) is a plasma cell neoplasm characterized by an abnormal proliferation of clonal, terminally differentiated B lymphocytes. Current approaches for the treatment of MM focus on developing new diagnostic techniques; however, the search for prognostic markers is also crucial. This enables the classification of patients into risk groups and, thus, the selection of the most optimal treatment method. Read More

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