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      Coding Cell Identity of Human Skeletal Muscle Progenitor Cells Using Cell Surface Markers: Current Status and Remaining Challenges for Characterization and Isolation

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          Abstract

          Skeletal muscle progenitor cells (SMPCs), also called myogenic progenitors, have been studied extensively in recent years because of their promising therapeutic potential to preserve and recover skeletal muscle mass and function in patients with cachexia, sarcopenia, and neuromuscular diseases. SMPCs can be utilized to investigate the mechanisms of natural and pathological myogenesis via in vitro modeling and in vivo experimentation. While various types of SMPCs are currently available from several sources, human pluripotent stem cells (PSCs) offer an efficient and cost-effective method to derive SMPCs. As human PSC-derived cells often display varying heterogeneity in cell types, cell enrichment using cell surface markers remains a critical step in current procedures to establish a pure population of SMPCs. Here we summarize the cell surface markers currently being used to detect human SMPCs, describing their potential application for characterizing, identifying and isolating human PSC-derived SMPCs. To date, several positive and negative markers have been used to enrich human SMPCs from differentiated PSCs by cell sorting. A careful analysis of current findings can broaden our understanding and reveal potential uses for these surface markers with SMPCs.

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          Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche.

          In adult skin, each hair follicle contains a reservoir of stem cells (the bulge), which can be mobilized to regenerate the new follicle with each hair cycle and to reepithelialize epidermis during wound repair. Here we report new methods that permit their clonal analyses and engraftment and demonstrate the two defining features of stem cells, namely self-renewal and multipotency. We also show that, within the bulge, there are two distinct populations, one of which maintains basal lamina contact and temporally precedes the other, which is suprabasal and arises only after the start of the first postnatal hair cycle. This spatial distinction endows them with discrete transcriptional programs, but surprisingly, both populations are growth inhibited in the niche but can self-renew in vitro and make epidermis and hair when grafted. These findings suggest that the niche microenvironment imposes intrinsic "stemness" features without restricting the establishment of epithelial polarity and changes in gene expression.
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            Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud.

            Limb muscles develop from cells that migrate from the somites. The signal that induces migration of myogenic precursor cells to the limb emanates from the mesenchyme of the limb bud. Here we report that the c-met-encoded receptor tyrosine kinase is essential for migration of myogenic precursor cells into the limb anlage and for migration into diaphragm and tip of tongue. In c-met homozygous mutant (-/-) mouse embryos, the limb bud and diaphragm are not colonized by myogenic precursor cells and, as a consequence, skeletal muscles of the limb and diaphragm do not form. In contrast, development of the axial skeletal muscles proceeds in the absence of c-met signalling. The specific ligand of the c-met protein, the motility and growth factor scatter factor/hepatocyte growth factor, is expressed in limb mesenchyme and can thus provide the signal for migration which is received by c-met. We have therefore identified a paracrine signalling system that regulates migration of myogenic precursor cells.
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              Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene.

              A novel potential cell surface receptor of the tyrosine kinase gene family has been identified and characterized by molecular cloning. Its primary sequence is very similar to that of the human epidermal growth factor receptor and the v-erbB oncogene product; the chromosomal location of the gene for this protein is coincident with the neu oncogene, which suggests that the two genes may be identical.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                26 November 2019
                2019
                : 7
                : 284
                Affiliations
                [1] 1Department of Comparative Biosciences, University of Wisconsin , Madison, WI, United States
                [2] 2The Stem Cell and Regenerative Medicine Center, University of Wisconsin , Madison, WI, United States
                Author notes

                Edited by: Atsushi Asakura, University of Minnesota Twin Cities, United States

                Reviewed by: Akiyoshi Uezumi, Tokyo Metropolitan Institute of Gerontology, Japan; So-ichiro Fukada, Osaka University, Japan

                *Correspondence: Masatoshi Suzuki masatoshi.suzuki@ 123456wisc.edu

                This article was submitted to Stem Cell Research, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2019.00284
                6890603
                31828070
                f262f53a-b63c-42b3-a465-102ce62e3d14
                Copyright © 2019 Tey, Robertson, Lynch and Suzuki.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 June 2019
                : 01 November 2019
                Page count
                Figures: 0, Tables: 3, Equations: 0, References: 177, Pages: 27, Words: 22064
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Funded by: Amyotrophic Lateral Sclerosis Association 10.13039/100000971
                Funded by: University of Wisconsin Foundation 10.13039/100011089
                Categories
                Cell and Developmental Biology
                Review

                skeletal muscle,skeletal muscle progenitor cells,cell surface markers,human pluripotent stem cells,human induced pluripotent stem cells,muscular dystrophy,neuromuscular diseases

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