The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Jonathan R Beauchamp - One of the best experts on this subject based on the ideXlab platform.
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the skeletal muscle satellite Cell Stem Cell or son of Stem Cell
Differentiation, 2001Co-Authors: Peter S Zammit, Jonathan R BeauchampAbstract:The concept of the adult tissue Stem Cell is fundamental to models of persistent renewal in functionally post-mitotic tissues. Although relatively ignored by Stem Cell biology, skeletal muscle is a prime example of an adult tissue that can generate terminally differentiated Cells uniquely specialized to carry out tissue-Specific functions. This capacity is attributed to satellite Cells, a population of undifferentiated, quiescent precursors that become activated to divide and differentiate in response to the demands of growth or damage. The aim of this review is to discuss the role of the satellite Cell as an adult tissue-Specific Stem Cell. We examine evidence for the presence of behaviourally and phenotypically distinct subpopulations of precursor within the satellite Cell pool. Further, we speculate on the possible identity, origins and relevance of multipotent muscle Stem Cells, a population with both myogenic and hematopoietic potentials that has been isolated from whole muscle. Taken together, current evidence suggests the possibility that the regenerative compartment of adult skeletal muscle may conform to an archetypal Stem Cell-based hierarchy, maintained within a Stem Cell niche. It therefore remains to be seen whether all satellite Cells are skeletal muscle-Specific Stem Cells, or whether some or all are the progeny of an as yet unidentified muscle Stem Cell.
Margaret Buckingham - One of the best experts on this subject based on the ideXlab platform.
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an adult tissue Specific Stem Cell in its niche a gene profiling analysis of in vivo quiescent and activated muscle satellite Cells
Stem Cell Research, 2010Co-Authors: Giorgia Pallafacchina, Stephanie Francois, Beatrice Regnault, Bertrand Czarny, Vincent Dive, Ana Cumano, Didier Montarras, Margaret BuckinghamAbstract:Abstract The satellite Cell of skeletal muscle provides a paradigm for quiescent and activated tissue Stem Cell states. We have carried out transcriptome analyses on satellite Cells purified by flow cytometry from Pax3 GFP/+ mice. We compared samples from adult skeletal muscles where satellite Cells are mainly quiescent, with samples from growing muscles or regenerating ( mdx ) muscles, where they are activated. Analysis of regulation that is shared by both activated states avoids other effects due to immature or pathological conditions. This in vivo profile differs from that of previously analyzed satellite Cells activated after Cell culture. It reveals how the satellite Cell protects itself from damage and maintains quiescence, while being primed for activation on receipt of the appropriate signal. This is illustrated by manipulation of the corepressor Dach1, and by the demonstration that quiescent satellite Cells are better protected from oxidative stress than those from mdx or 1-week-old muscles. The quiescent versus in vivo activated comparison also gives new insights into how the satellite Cell controls its niche on the muscle fiber through Cell adhesion and matrix remodeling. The latter also potentiates growth factor activity through proteoglycan modification. Dismantling the extraCellular matrix is important for satellite Cell activation when the expression of proteinases is up-regulated, whereas transcripts for their inhibitors are high in quiescent Cells. In keeping with this, we demonstrate that metalloproteinase function is required for efficient regeneration in vivo .
S Tsang - One of the best experts on this subject based on the ideXlab platform.
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validation of genome wide association study gwas identified disease risk alleles with patient Specific Stem Cell lines
Human Molecular Genetics, 2014Co-Authors: Jin Yang, Lawrence W C Chan, Yiting Tsai, Huy V Nguyen, Chunwei Hsu, Lewis M Brown, Dieter Egli, Janet R Sparrow, S TsangAbstract:While the past decade has seen great progress in mapping loci for common diseases, studying how these risk alleles lead to pathology remains a challenge. Age-related macular degeneration (AMD) affects 9 million older Americans, and is characterized by the loss of the retinal pigment epithelium (RPE). Although the closely linked genome-wide association studies ARMS2/HTRA1 genes, located at the chromosome 10q26 locus, are strongly associated with the risk of AMD, their downstream targets are unknown. Low population frequencies of risk alleles in tissue banks make it impractical to study their function in Cells derived from autopsied tissue. Moreover, autopsy eyes from end-stage AMD patients, where age-related RPE atrophy and fibrosis are already present, cannot be used to determine how abnormal ARMS2/HTRA1 expression can initiate RPE pathology. Instead, induced pluripotent Stem (iPS) Cell-derived RPE from patients provides us with earlier stage AMD patient-Specific Cells and allows us to analyze the underlying mechanisms at this critical time point. An unbiased proteome screen of A2E-aged patient-Specific iPS-derived RPE Cell lines identified superoxide dismutase 2 (SOD2)-mediated antioxidative defense in the genetic allele's susceptibility of AMD. The AMD-associated risk haplotype (T-in/del-A) impairs the ability of the RPE to defend against aging-related oxidative stress. SOD2 defense is impaired in RPE homozygous for the risk haplotype (T-in/del-A; T-in/del-A), while the effect was less pronounced in RPE homozygous for the protective haplotype (G-Wt-G; G-Wt-G). ARMS2/HTRA1 risk alleles decrease SOD2 defense, making RPE more susceptible to oxidative damage and thereby contributing to AMD pathogenesis.
Irving L. Weissman - One of the best experts on this subject based on the ideXlab platform.
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establishment of a normal hematopoietic and leukemia Stem Cell hierarchy
Cold Spring Harbor Symposia on Quantitative Biology, 2008Co-Authors: Mark P Chao, Jun Seita, Irving L. WeissmanAbstract:Many types of adult tissues, especially for high turnover tissues such as the blood and intestinal syStem, stand on a hierarchical tissue-Specific Stem Cell syStem. Tissue-Specific Stem Cells concurrently have self-renewal capacity and potential to give rise to all types of mature Cells in their tissue. The differentiation process of the tissue-Specific Stem Cell is successive restriction of these capacities. The first progeny of tissue-Specific Stem Cells are multipotent progenitors (MPPs) that lose long-term self-renewal capacity yet have full lineage potential. MPPs in turn give rise to oligopotent progenitors, which then commit into lineage-restricted progenitors. This hierarchical syStem enables a lifelong supply of matured functional Cells that generally have a short life span and a relatively high turnover rate. In this chapter, we review our findings and other key experiments that have led to the establishment of the current Cellular Stem and progenitor hierarchy in the blood-forming syStems of mice and humans for both normal and leukemic hematopoiesis. We also review select signaling pathways intrinsic to normal hematopoietic and leukemic Stem Cell populations as well our recent findings elucidating the possible origin of the leukemia Stem Cell.
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Hematopoietic Stem Cells: the paradigmatic tissue-Specific Stem Cell
American Journal of Pathology, 2006Co-Authors: David Bryder, Derrick J. Rossi, Irving L. WeissmanAbstract:The recent prospective isolation of a wide variety of somatically derived Stem Cells has affirmed the notion that homeostatic maintenance of most tissues and organs is mediated by tissue-Specific Stem and progenitor Cells and fueled enthusiasm for the use of such Cells in strategies aimed at repairing or replacing damaged, diseased, or genetically deficient tissues and organs. Hematopoietic Stem Cells (HSCs) are arguably the most well-characterized tissue-Specific Stem Cell, with decades of basic research and clinical application providing not only a profound understanding of the principles of Stem Cell biology, but also of its potential pitfalls. It is our belief that emerging Stem Cell fields can benefit greatly from an understanding of the lessons learned from the study of HSCs. In this review we discuss some general concepts regarding Stem Cell biology learned from the study of HSCs with a highlight on recent work pertaining to emerging topics of interest for Stem Cell biology.
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biological perspectives hematopoietic Stem Cells the paradigmatic tissue Specific Stem Cell
2006Co-Authors: David Bryder, Derrick J. Rossi, Irving L. WeissmanAbstract:The recent prospective isolation of a wide variety of somatically derived Stem Cells has affirmed the notion that homeostatic maintenance of most tissues and organs is mediated by tissue-Specific Stem and progenitor Cells and fueled enthusiasm for the use of such Cells in strategies aimed at repairing or replacing damaged, diseased, or genetically deficient tissues and organs. Hematopoietic Stem Cells (HSCs) are arguably the most well-characterized tissue-Specific Stem Cell , with decades of basic research and clinical application providing not only a profound understanding of the principles of Stem Cell biology, but also of its potential pitfalls. It is our belief that emerging Stem Cell fields can benefit greatly from an understanding of the lessons learned from the study of HSCs. In this review we discuss some general concepts regarding Stem Cell biology learned from the study of HSCs with a highlight on recent work pertaining to emerging topics of interest for Stem Cell biology. (Am J Pathol 2006, 169:338–346; DOI: 10.2353/ajpath.2006.060312)
Peter S Zammit - One of the best experts on this subject based on the ideXlab platform.
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the skeletal muscle satellite Cell Stem Cell or son of Stem Cell
Differentiation, 2001Co-Authors: Peter S Zammit, Jonathan R BeauchampAbstract:The concept of the adult tissue Stem Cell is fundamental to models of persistent renewal in functionally post-mitotic tissues. Although relatively ignored by Stem Cell biology, skeletal muscle is a prime example of an adult tissue that can generate terminally differentiated Cells uniquely specialized to carry out tissue-Specific functions. This capacity is attributed to satellite Cells, a population of undifferentiated, quiescent precursors that become activated to divide and differentiate in response to the demands of growth or damage. The aim of this review is to discuss the role of the satellite Cell as an adult tissue-Specific Stem Cell. We examine evidence for the presence of behaviourally and phenotypically distinct subpopulations of precursor within the satellite Cell pool. Further, we speculate on the possible identity, origins and relevance of multipotent muscle Stem Cells, a population with both myogenic and hematopoietic potentials that has been isolated from whole muscle. Taken together, current evidence suggests the possibility that the regenerative compartment of adult skeletal muscle may conform to an archetypal Stem Cell-based hierarchy, maintained within a Stem Cell niche. It therefore remains to be seen whether all satellite Cells are skeletal muscle-Specific Stem Cells, or whether some or all are the progeny of an as yet unidentified muscle Stem Cell.