212 results match your criteria step dedifferentiation


Differentiation of human adult-derived stem cells towards a neural lineage involves a dedifferentiation event prior to differentiation to neural phenotypes.

Sci Rep 2021 Jun 8;11(1):12034. Epub 2021 Jun 8.

Instituto de Neurociencias de Alicante (UMH-CSIC), Campus de San Juan, 03550, Alicante, Spain.

Although it has been reported that mesenchymal stem cells isolated from adult tissues can be induced to overcome their mesenchymal fate and transdifferentiate into neural cells, the findings and their interpretation have been challenged. The main argument against this process is that the cells rapidly adopt neuron-like morphologies through retraction of the cytoplasm rather than active neurite extension. In this study, we examined the sequence of biological events during neural differentiation of human periodontal ligament-derived stem cells (hPDLSCs), human bone marrow-derived stem cells (hBMSCs) and human dental pulp-derived stem cells (hDPSCs) by time-lapse microscopy. Read More

View Article and Full-Text PDF

Autophagy suppresses the formation of hepatocyte-derived cancer-initiating ductular progenitor cells in the liver.

Sci Adv 2021 Jun 4;7(23). Epub 2021 Jun 4.

Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.

Hepatocellular carcinoma (HCC) is driven by repeated rounds of inflammation, leading to fibrosis, cirrhosis, and, ultimately, cancer. A critical step in HCC formation is the transition from fibrosis to cirrhosis, which is associated with a change in the liver parenchyma called ductular reaction. Here, we report a genetically engineered mouse model of HCC driven by loss of macroautophagy and hemizygosity of phosphatase and tensin homolog, which develops HCC involving ductular reaction. Read More

View Article and Full-Text PDF

Isolation of Mouse Interstitial Valve Cells to Study the Calcification of the Aortic Valve In Vitro.

J Vis Exp 2021 May 10(171). Epub 2021 May 10.

Cardiovascular Research Center, The Icahn School of Medicine at Mount Sinai; Diabetes, Obesity and Metabolism Institute, Department of Medicine, The Icahn School of Medicine at Mount Sinai; Graduate School of Biomedical Sciences, The Icahn School of Medicine at Mount Sinai.

The calcification of aortic valve cells is the hallmark of aortic stenosis and is associated with valve cusp fibrosis. Valve interstitial cells (VICs) play an important role in the calcification process in aortic stenosis through the activation of their dedifferentiation program to osteoblast-like cells. Mouse VICs are a good in vitro tool for the elucidation of the signaling pathways driving the mineralization of the aortic valve cell. Read More

View Article and Full-Text PDF

Crosstalk Between Mesenchymal Stromal Cells and Chondrocytes: The Hidden Therapeutic Potential for Cartilage Regeneration.

Stem Cell Rev Rep 2021 May 5. Epub 2021 May 5.

AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos Platz, Switzerland.

Cartilage injuries following trauma create a puzzling clinical scenario. The finite reparative potential of articular cartilage is well known, and injuries are associated with an increased risk of osteoarthritis. Cell-based therapies have spotlighted chondrocytes and mesenchymal stromal cells (MSCs) as the functional unit of articular cartilage and the progenitor cells, respectively. Read More

View Article and Full-Text PDF

Cancer cells retrace a stepwise differentiation program during malignant progression.

Cancer Discov 2021 Apr 28. Epub 2021 Apr 28.

Swiss Inst. for Exp. Cancer Res. (ISREC)

Pancreatic Neuroendocrine Tumors (PanNETs) comprise two molecular subtypes, relatively benign islet tumors (IT) and invasive, metastasis-like primary (MLP) tumors. Hitherto, the origin of aggressive MLP tumors has been obscure. Herein, using multi-omics approaches, we revealed that MLP tumors arise from IT via dedifferentiation following a reverse trajectory along the developmental pathway of islet B-cells, which results in the acquisition of a progenitor-like molecular phenotype. Read More

View Article and Full-Text PDF

Reactivation of the Hedgehog pathway in esophageal progenitors turns on an embryonic-like program to initiate columnar metaplasia.

Cell Stem Cell 2021 Apr 14. Epub 2021 Apr 14.

IRIBHM, ULB/Faculty of Medicine, 808 route de Lennik, 1070 Brussels, Belgium; WELBIO/FNRS Principal Investigator at IRIBHM, ULB/Faculty of Medicine, 808 route de Lennik, 1070 Brussels, Belgium. Electronic address:

Columnar metaplasia of the esophagus is the main risk factor for esophageal adenocarcinoma. There is a lack of evidence to demonstrate that esophageal progenitors can be the source of columnar metaplasia. In this study, using transgenic mouse models, lineage tracing, single-cell RNA sequencing, and transcriptomic and epigenetic profiling, we found that the activation of the Hedgehog pathway in esophageal cells modifies their differentiation status in vivo. Read More

View Article and Full-Text PDF

100 years of iodine testing of the cervix: A critical review and implications for the future.

Eur J Obstet Gynecol Reprod Biol 2021 Jun 14;261:34-40. Epub 2021 Apr 14.

Department of Obstetrics & Gynecology, Medical University of Graz, Austria.

Objectives: We aim to describe the history of iodine testing of the cervix and identify areas where further work is required.

Study Design: We conducted a search of PubMed and Google Scholar. Full article texts were reviewed. Read More

View Article and Full-Text PDF

N-Glycan profiling of chondrocytes and fibroblast-like synoviocytes: Towards functional glycomics in osteoarthritis.

Proteomics Clin Appl 2021 May 12;15(2-3):e2000057. Epub 2021 Mar 12.

Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.

Purpose: N-Glycan profiling provides an indicator of the cellular potential for functional pairing with tissue lectins. Following the discovery of galectin expression by chondrocytes as a factor in osteoarthritis pathobiology, mapping of N-glycans upon their phenotypic dedifferentiation in culture and in fibroblast-like synoviocytes is a step to better understand glycobiological contributions to disease progression.

Experimental Design: The profiles of cellular N-glycans of human osteoarthritic chondrocytes and fibroblast-like synoviocytes were characterized by mass spectrometry. Read More

View Article and Full-Text PDF

Cellular plasticity at the nexus of development and disease.

Development 2021 Feb 5;148(3). Epub 2021 Feb 5.

Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA

In October 2020, the Keystone Symposia Global Health Series hosted a Keystone eSymposia entitled 'Tissue Plasticity: Preservation and Alteration of Cellular Identity'. The event synthesized groundbreaking research from unusually diverse fields of study, presented in various formats, including live and virtual talks, panel discussions and interactive e-poster sessions. The meeting focused on cell identity changes and plasticity in multiple tissues, species and developmental contexts, both in homeostasis and during injury. Read More

View Article and Full-Text PDF
February 2021

Arthroscopic Minced Cartilage Implantation (MCI): A Technical Note.

Arthrosc Tech 2021 Jan 19;10(1):e97-e101. Epub 2020 Dec 19.

Gelenkzentrum Rhein-Main, Wiesbaden, Germany.

Articular cartilage lesions are identified with increasing frequency. Several cartilage repair techniques are available to treat symptomatic cartilage defects. The ultimate goal of any cartilage repair procedure is the prevention of premature osteoarthritis. Read More

View Article and Full-Text PDF
January 2021

lncRNA Blocks the Shot of Breast Cancer Cells Self-Renewal Mechanism.

Cancer Res 2021 02;81(3):535-536

Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.

The study by Zagorac and colleagues represents an important step forward in the field of breast cancer, explaining a novel molecular mechanism of transition from slowly multiplying tumor-initiating cells (TIC) into their more differentiated version characterized by high proliferation. The mechanism involves the transcription factors SOX2 and EZH2, which directly repress transcription of cell-cycle genes and activate self-renewal genes in breast cancer cells. This mechanism is further controlled by a negative feedback loop mediated by a long noncoding RNA, , not described previously, which is upregulated in tumorspheres and inhibits SOX2 and EZH2. Read More

View Article and Full-Text PDF
February 2021

Mesenchymal Stem Cell-Secreted Extracellular Vesicles Instruct Stepwise Dedifferentiation of Breast Cancer Cells into Dormancy at the Bone Marrow Perivascular Region.

Cancer Res 2021 03 26;81(6):1567-1582. Epub 2021 Jan 26.

Rutgers School of Graduate Studies at New Jersey Medical School, Newark, New Jersey.

In the bone marrow (BM), breast cancer cells (BCC) can survive in dormancy for decades as cancer stem cells (CSC), resurging as tertiary metastasis. The endosteal region where BCCs exist as CSCs poses a challenge to target them, mostly due to the coexistence of endogenous hematopoietic stem cells. This study addresses the early period of dormancy when BCCs enter BM at the perivascular region to begin the transition into CSCs, which we propose as the final step in dormancy. Read More

View Article and Full-Text PDF

Transcriptional activators YAP/TAZ and AXL orchestrate dedifferentiation, cell fate, and metastasis in human osteosarcoma.

Cancer Gene Ther 2021 Jan 6. Epub 2021 Jan 6.

Sarcoma Medical Oncology Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Osteosarcoma (OS) is a molecularly heterogeneous, aggressive, poorly differentiated pediatric bone cancer that frequently spreads to the lung. Relatively little is known about phenotypic and epigenetic changes that promote lung metastases. To identify key drivers of metastasis, we studied human CCH-OS-D OS cells within a previously described rat acellular lung (ACL) model that preserves the native lung architecture, extracellular matrix, and capillary network. Read More

View Article and Full-Text PDF
January 2021

Transcriptome analysis identifies genes involved in the somatic embryogenesis of Eucalyptus.

BMC Genomics 2020 Nov 18;21(1):803. Epub 2020 Nov 18.

Guangxi Key Laboratory of Superior Timber Trees Resource Cultivation, Guangxi Forestry Research Institute, 23 Yongwu Road, Nanning, 530002, Guangxi, China.

Background: Eucalyptus, a highly diverse genus of the Myrtaceae family, is the most widely planted hardwood in the world due to its increasing importance for fiber and energy. Somatic embryogenesis (SE) is one large-scale method to provide commercial use of the vegetative propagation of Eucalyptus and dedifferentiation is a key step for plant cells to become meristematic. However, little is known about the molecular changes during the Eucalyptus SE. Read More

View Article and Full-Text PDF
November 2020

Dedifferentiation and neuronal repression define familial Alzheimer's disease.

Sci Adv 2020 Nov 13;6(46). Epub 2020 Nov 13.

Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.

Identifying the systems-level mechanisms that lead to Alzheimer's disease, an unmet need, is an essential step toward the development of therapeutics. In this work, we report that the key disease-causative mechanisms, including dedifferentiation and repression of neuronal identity, are triggered by changes in chromatin topology. Here, we generated human induced pluripotent stem cell (hiPSC)-derived neurons from donor patients with early-onset familial Alzheimer's disease (EOFAD) and used a multiomics approach to mechanistically characterize the modulation of disease-associated gene regulatory programs. Read More

View Article and Full-Text PDF
November 2020

A 3D Cell Culture Model Identifies Wnt/-Catenin Mediated Inhibition of p53 as a Critical Step during Human Hepatocyte Regeneration.

Adv Sci (Weinh) 2020 Aug 23;7(15):2000248. Epub 2020 Jun 23.

Department of Physiology and Pharmacology Karolinska Institutet Stockholm 171 77 Sweden.

The liver is a highly regenerative organ. While mature hepatocytes under homeostatic conditions are largely quiescent, upon injury, they rapidly enter the cell cycle to recover the damaged tissue. In rodents, a variety of injury models have provided important insights into the molecular underpinnings that govern the proliferative activation of quiescent hepatocytes. Read More

View Article and Full-Text PDF

Overexpression of early T cell differentiation-specific transcription factors transforms the terminally differentiated effector T cells into less differentiated state.

Cell Immunol 2020 07 6;353:104118. Epub 2020 May 6.

Guangdong Province Key Laboratory of Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou, China; School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China. Electronic address:

The in vivo proliferation and viability of transfused engineered T cells markedly limits the long-term effect of adoptive cell therapy on tumors. The therapeutic efficacy and proliferative potential of T cells are reported to be dependent on the differentiation status of T cells. The T cells at the early stage of progressive differentiation have a long lifespan, strong proliferative potential, and the ability to reconstruct intact T cell subsets. Read More

View Article and Full-Text PDF

Dynamic Transcriptome Analysis Reveals Uncharacterized Complex Regulatory Pathway Underlying Genotype-Recalcitrant Somatic Embryogenesis Transdifferentiation in Cotton.

Genes (Basel) 2020 05 7;11(5). Epub 2020 May 7.

State Key Laboratory of Crop Biology, College of Agronomy, Shandong Agricultural University, Tai'an 271018, China.

As a notable illustration of totipotency and plant regeneration, somatic embryogenesis (SE) is the developmental reprogramming of somatic cells toward the embryogenesis pathway, the key step for genetic engineering. Investigations examining the totipotency process are of great fundamental and practical importance in crop biotechnology. However, high-frequency regeneration of cotton via SE has been limited due to genotype-dependent response. Read More

View Article and Full-Text PDF

The role of DNA demethylation in induction of stem cells.

Prog Biophys Mol Biol 2020 07 1;153:17-22. Epub 2020 Jan 1.

Genetics, Stem Cells, Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, 1983963113, Iran. Electronic address:

DNA methylation is an epigenetic factor, which plays important roles in embryo and many other diseases development. This factor determines gene expression, and when half of them have CpG islands, DNA methylation and its enzyme effectors have been under the vast studies. Whole genome DNA demethylation is a crucial step of embryogenesis and also cell fate determination in embryos. Read More

View Article and Full-Text PDF

Critical Role of Cytosolic DNA and Its Sensing Adaptor STING in Aortic Degeneration, Dissection, and Rupture.

Circulation 2020 01 30;141(1):42-66. Epub 2019 Dec 30.

Cardiovascular Research Institute (J.S.C., S.A.L., Y.H.S.), Baylor College of Medicine, Houston, TX.

Background: Sporadic aortic aneurysm and dissection (AAD), caused by progressive aortic smooth muscle cell (SMC) loss and extracellular matrix degradation, is a highly lethal condition. Identifying mechanisms that drive aortic degeneration is a crucial step in developing an effective pharmacologic treatment to prevent disease progression. Recent evidence has indicated that cytosolic DNA and abnormal activation of the cytosolic DNA sensing adaptor STING (stimulator of interferon genes) play a critical role in vascular inflammation and destruction. Read More

View Article and Full-Text PDF
January 2020

Death versus dedifferentiation: The molecular bases of beta cell mass reduction in type 2 diabetes.

Authors:
Tong Sun Xiao Han

Semin Cell Dev Biol 2020 07 9;103:76-82. Epub 2019 Dec 9.

Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211100, People's Republic of China. Electronic address:

Diabetes Mellitus is currently affecting more than 425 million people worldwide, among which over 90 % of the cases belong to type 2 diabetes. The number is growing quickly every year. Together with its many complications, the disease is causing tremendous social and economic burden and is classified as one of the leading causes of high morbidity and mortality rate. Read More

View Article and Full-Text PDF

Gene expression markers in horse articular chondrocytes: Chondrogenic differentiaton IN VITRO depends on the proliferative potential and ageing. Implication for tissue engineering of cartilage.

Res Vet Sci 2020 Feb 6;128:107-117. Epub 2019 Nov 6.

Department of Veterinary Sciences, University of Parma, Italy.

Chondrocyte dedifferentiation is a key limitation in therapies based on autologous chondrocyte implantation for cartilage repair. Articular chondrocytes, obtained from (metacarpophalangeal and metatarsophalangeal) joints of different aged horses, were cultured in monolayer for several passages (P0 to P8). Cumulative Populations Doublings Levels (PDL) and gene expression of relevant chondrocyte phenotypic markers were analysed during culturing. Read More

View Article and Full-Text PDF
February 2020

Prognostic impact of CD34 and SMA in cancer-associated fibroblasts in stage I-III NSCLC.

Thorac Cancer 2020 01 24;11(1):120-129. Epub 2019 Nov 24.

Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, Muenster, Germany.

Background: Epithelial-to-mesenchymal transition (EMT) is a crucial step in lung cancer pathogenesis. Among others, cancer-associated fibroblasts (CAFs) are reported to regulate this process.

Objectives: To investigate the prognostic and clinical impact, we analyzed CD34+ and SMA+ CAFs in non-small cell lung cancer (NSCLC). Read More

View Article and Full-Text PDF
January 2020

The explant developmental stage profoundly impacts small RNA-mediated regulation at the dedifferentiation step of maize somatic embryogenesis.

Sci Rep 2019 10 10;9(1):14511. Epub 2019 Oct 10.

Departamento de Bioquímica, Facultad de Química, Universidad Nacional Autónoma de México, CDMX, 04510, México.

Maize somatic embryogenesis (SE) requires the induction of embryogenic callus and establishment of proliferation before plant regeneration. The molecular mechanisms underlying callus embryogenic potential are not well understood. Here we explored the role of small RNAs (sRNAs) and the accumulation of their target transcripts in maize SE at the dedifferentiation step using VS-535 zygotic embryos collected at distinct developmental stages and displaying contrasting in vitro embryogenic potential and morphology. Read More

View Article and Full-Text PDF
October 2019

Yorkie and JNK revert syncytial muscles into myoblasts during Org-1-dependent lineage reprogramming.

J Cell Biol 2019 11 7;218(11):3572-3582. Epub 2019 Oct 7.

Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Biology, Division of Developmental Biology, Erlangen, Germany

Lineage reprogramming has received increased research attention since it was demonstrated that lineage-restricted transcription factors can be used in vitro for direct reprogramming. Recently, we reported that the ventral longitudinal musculature of the adult heart arises in vivo by direct lineage reprogramming from larval alary muscles, a process that starts with the dedifferentiation and fragmentation of syncytial muscle cells into mononucleate myoblasts and depends on Org-1 ( Tbx1). Here, we shed light on the events occurring downstream of Org-1 in this first step of transdifferentiation and show that alary muscle lineage-specific activation of Yorkie plays a key role in initiating the dedifferentiation and fragmentation of these muscles. Read More

View Article and Full-Text PDF
November 2019

Mouse Model of Thyroid Cancer Progression and Dedifferentiation Driven by STRN-ALK Expression and Loss of p53: Evidence for the Existence of Two Types of Poorly Differentiated Carcinoma.

Thyroid 2019 10 16;29(10):1425-1437. Epub 2019 Aug 16.

Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.

Thyroid tumor progression from well-differentiated cancer to poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) involves step-wise dedifferentiation associated with loss of iodine avidity and poor outcomes. fusions, typically , are found with higher incidence in human PDTC compared with well-differentiated cancer and, as previously shown, can drive the development of murine PDTC. The aim of this study was to evaluate thyroid cancer initiation and progression in mice with concomitant expression of and inactivation of the tumor suppressor () in thyroid follicular cells. Read More

View Article and Full-Text PDF
October 2019

A Protocol for One-Step Differentiation of Human Induced Pluripotent Stem Cells into Mature Podocytes.

Methods Mol Biol 2019 ;1994:93-99

Division of Molecular and Computational Toxicology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Within the glomerulus, podocytes are highly specialized visceral epithelial cells that are part of the glomerular filtration barrier. Human podocyte cell culture is rather challenging for primary or immortalized cells, due to the nonproliferative state of the cells. In addition, rapid dedifferentiation is often observed. Read More

View Article and Full-Text PDF

Context-Dependent Impact of RAS Oncogene Expression on Cellular Reprogramming to Pluripotency.

Stem Cell Reports 2019 05 2;12(5):1099-1112. Epub 2019 May 2.

Laboratorio de Células Madre en Cáncer y Envejecimiento, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), E15706 Santiago de Compostela, Spain. Electronic address:

Induction of pluripotency in somatic cells with defined genetic factors has been successfully used to investigate the mechanisms of disease initiation and progression. Cellular reprogramming and oncogenic transformation share common features; both involve undergoing a dramatic change in cell identity, and immortalization is a key step for cancer progression that enhances reprogramming. However, there are very few examples of complete successful reprogramming of tumor cells. Read More

View Article and Full-Text PDF

Glutathione prevents chronic oscillating glucose intake-induced β-cell dedifferentiation and failure.

Cell Death Dis 2019 04 11;10(4):321. Epub 2019 Apr 11.

Cardiac Regeneration Research Institute, Wenzhou Medical University, Wenzhou, China.

Modern lifestyles have altered diet and metabolic homeostasis, with increased sugar intake, glycemic index, and prediabetes. A strong positive correlation between sugar consumption and diabetic incidence is revealed, but the underlying mechanisms remain obscure. Here we show that oral intake of long-term oscillating glucose (LOsG) (4 times/day) for 38 days, which produces physiological glycemic variability in rats, can lead to β-cells gaining metabolic memory in reactive oxygen species (ROS) stress. Read More

View Article and Full-Text PDF

Regulation of long non-coding RNAs and circular RNAs in spermatogonial stem cells.

Reproduction 2019 07;158(1):R15-R25

Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Spermatogonial stem cells (SSCs) are one of the most significant stem cells with the potentials of self-renewal, differentiation, transdifferentiation and dedifferentiation, and thus, they have important applications in reproductive and regenerative medicine. They can transmit the genetic and epigenetic information across generations, which highlights the importance of the correct establishment and maintenance of epigenetic marks. Accurate transcriptional and post-transcriptional regulation is required to support the highly coordinated expression of specific genes for each step of spermatogenesis. Read More

View Article and Full-Text PDF