Topic
Cellular differentiation
About: Cellular differentiation is a research topic. Over the lifetime, 90966 publications have been published within this topic receiving 6099252 citations. The topic is also known as: Cellular differentiation & GO:0030154.
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TL;DR: It is proposed that the early expression of Pax4 in a subset of endocrine progenitors is essential for the differentiation of the β and δ cell lineages, and a default pathway would explain the elevated number of α cells in the absence of Pax 4.
Abstract: The mammalian pancreas contains two distinct cell populations: endocrine cells which secrete hormones into the bloodstream, and exocrine cells, which secrete enzymes into the digestive tract. The four endocrine cell types found in the adult pancreas-(alpha, beta, delta and PP-synthesize glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. All of these endocrine cells arise from common multipotent precursors, which coexpress several hormones when they start to differentiate. Expression of some homeobox genes in the early developing pancreas has been reported. The Pax4 gene is expressed in the early pancreas, but is later restricted to beta cells. Inactivation of Pax4 by homologous recombination results in the absence of mature insulin- and somatostatin-producing cells (beta and delta, respectively) in the pancreas of Pax4 homozygous mutant mice, but glucagon-producing alpha cells are present in considerably higher numbers. We propose that the early expression of Pax4 in a subset of endocrine progenitors is essential for the differentiation of the beta and delta cell lineages. A default pathway would explain the elevated number of alpha cells in the absence of Pax4.
803 citations
TL;DR: Data demonstrated a paracrine but not autocrine regulation of the growth and differentiation of myeloma cells by IL-6, which is not the autocrine growth factor of these well-documented human myelomatic cell lines.
803 citations
TL;DR: It is demonstrated that the PTEN tumor suppressor plays an important role in regulating neural stem/progenitor cells in vivo and in vitro, and results suggest that PTEN negatively regulates neural stem cell proliferation.
Abstract: The mechanisms controlling neural stem cell proliferation are poorly understood. Here we demonstrate that the PTEN tumor suppressor plays an important role in regulating neural stem/progenitor cells in vivo and in vitro. Mice lacking PTEN exhibited enlarged, histoarchitecturally abnormal brains, which resulted from increased cell proliferation, decreased cell death, and enlarged cell size. Neurosphere cultures revealed a greater proliferation capacity for tripotent Pten-/- central nervous system stem/progenitor cells, which can be attributed, at least in part, to a shortened cell cycle. However, cell fate commitments of the progenitors were largely undisturbed. Our results suggest that PTEN negatively regulates neural stem cell proliferation.
801 citations
TL;DR: Monoclonal antibodies are generated that distinguish among major cell types present during mammalian neurogenesis, and these antibodies have been used to analyze the development of cellular organization in the early nervous system.
Abstract: A major difficulty in studying early developmental processes and testing hypotheses of possible cellular mechanisms of development has been the inability to reproducibly identify specific cell types. We have generated monoclonal antibodies that distinguish among major cell types present during mammalian neurogenesis. These antibodies have been used to analyze the development of cellular organization in the early nervous system. Monoclonal antibody Rat-401 identifies a transient radial glial cell in the embryonic rat central nervous system (CNS) that is temporally and spatially suited to guide neuronal migration. Rat-401 also identifies a peripheral non-neuronal cell that may establish axon routes from the CNS to the periphery. Monoclonal antibody Rat-202 recognizes an antigen present in early axons, their growth cones, and filopodia, and has allowed us to follow early axons and observe the structures they contact. Two other antibodies that recognize axons demonstrate antigenically distinct phases in axon development. In addition, we report a marker for another cell class present in the developing nervous system, the endothelial cells that give rise to the CNS vasculature.
801 citations
TL;DR: It is found that the age-PCGT methylation signature is present in preneoplastic conditions and may drive gene expression changes associated with carcinogenesis in normal and cancer solid tissues and a population of bone marrow mesenchymal stem/stromal cells.
Abstract: Polycomb group proteins (PCGs) are involved in repression of genes that are required for stem cell differentiation. Recently, it was shown that promoters of PCG target genes (PCGTs) are 12-fold more likely to be methylated in cancer than non-PCGTs. Age is the most important demographic risk factor for cancer, and we hypothesized that its carcinogenic potential may be referred by irreversibly stabilizing stem cell features. To test this, we analyzed the methylation status of over 27,000 CpGs mapping to promoters of approximately 14,000 genes in whole blood samples from 261 postmenopausal women. We demonstrate that stem cell PCGTs are far more likely to become methylated with age than non-targets (odds ratio = 5.3 [3.8-7.4], P < 10(-10)), independently of sex, tissue type, disease state, and methylation platform. We identified a specific subset of 69 PCGT CpGs that undergo hypermethylation with age and validated this methylation signature in seven independent data sets encompassing over 900 samples, including normal and cancer solid tissues and a population of bone marrow mesenchymal stem/stromal cells (P < 10(-5)). We find that the age-PCGT methylation signature is present in preneoplastic conditions and may drive gene expression changes associated with carcinogenesis. These findings shed substantial novel insights into the epigenetic effects of aging and support the view that age may predispose to malignant transformation by irreversibly stabilizing stem cell features.
801 citations