Asymmetric Self-Renewal and Commitment of Satellite Stem Cells in Muscle
Satellite cells play a central role in mediating the growth and regeneration of skeletal muscle. However, whether satellite cells are stem cells, committed progenitors, or dedifferentiated myoblasts has remained unclear. Using Myf5-Cre and ROSA26-YFP Cre-reporter alleles, we observed that in vivo 10...
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Veröffentlicht in: | Cell 2007-06, Vol.129 (5), p.999-1010 |
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description | Satellite cells play a central role in mediating the growth and regeneration of skeletal muscle. However, whether satellite cells are stem cells, committed progenitors, or dedifferentiated myoblasts has remained unclear. Using Myf5-Cre and ROSA26-YFP Cre-reporter alleles, we observed that in vivo 10% of sublaminar Pax7-expressing satellite cells have never expressed Myf5. Moreover, we found that Pax7+/Myf5− satellite cells gave rise to Pax7+/Myf5+ satellite cells through apical-basal oriented divisions that asymmetrically generated a basal Pax7+/Myf5− and an apical Pax7+/Myf5+ cells. Prospective isolation and transplantation into muscle revealed that whereas Pax7+/Myf5+ cells exhibited precocious differentiation, Pax7+/Myf5− cells extensively contributed to the satellite cell reservoir throughout the injected muscle. Therefore, we conclude that satellite cells are a heterogeneous population composed of stem cells and committed progenitors. These results provide critical insights into satellite cell biology and open new avenues for therapeutic treatment of neuromuscular diseases. |
doi_str_mv | 10.1016/j.cell.2007.03.044 |
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However, whether satellite cells are stem cells, committed progenitors, or dedifferentiated myoblasts has remained unclear. Using Myf5-Cre and ROSA26-YFP Cre-reporter alleles, we observed that in vivo 10% of sublaminar Pax7-expressing satellite cells have never expressed Myf5. Moreover, we found that Pax7+/Myf5− satellite cells gave rise to Pax7+/Myf5+ satellite cells through apical-basal oriented divisions that asymmetrically generated a basal Pax7+/Myf5− and an apical Pax7+/Myf5+ cells. Prospective isolation and transplantation into muscle revealed that whereas Pax7+/Myf5+ cells exhibited precocious differentiation, Pax7+/Myf5− cells extensively contributed to the satellite cell reservoir throughout the injected muscle. Therefore, we conclude that satellite cells are a heterogeneous population composed of stem cells and committed progenitors. These results provide critical insights into satellite cell biology and open new avenues for therapeutic treatment of neuromuscular diseases.</description><subject>Animals</subject><subject>Cell Differentiation</subject><subject>Cell Separation</subject><subject>Cell Transplantation</subject><subject>Female</subject><subject>HUMDISEASE</subject><subject>Luminescent Proteins - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Muscle, Skeletal - cytology</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Myogenic Regulatory Factor 5 - metabolism</subject><subject>PAX7 Transcription Factor - metabolism</subject><subject>Receptors, Notch - metabolism</subject><subject>Satellite Cells, Skeletal Muscle - cytology</subject><subject>Satellite Cells, Skeletal Muscle - metabolism</subject><subject>STEMCELL</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd1rFDEUxYModq3-Az5Innyb6U0mmSQgQlnUFloKXX0O2cyNZpmPOsm29L83wy5-vNinEPI7J_eeQ8hbBjUD1p7tao99X3MAVUNTgxDPyIqBUZVgij8nKwDDK90qcUJepbQDAC2lfElOmJICmNIrcnGeHocB8xw93WAfqlsc8cH11I0dXU_DEPOAY6ZToBuXy3cxI91kHOi6XBKNI73eJ9_ja_IiuD7hm-N5Sr59_vR1fVFd3Xy5XJ9fVV5KyBXXyJVpO6OE2XrsWokhoNPbxnnjOGCnt6E13gvN26ARUErBvIHQNUI7bE7Jx4Pv3X47YOfLcLPr7d0cBzc_2slF--_LGH_Y79O95YppJaAYvD8azNPPPaZsh5iWIN2I0z5ZBSUjzvWTIF_yNK0pID-Afp5SmjH8noaBXZqyO7voFoWy0NjSVBG9-3uPP5JjNQX4cACwpHkfcbbJRxxLZnFGn203xf_5_wLK_6Y4</recordid><startdate>20070601</startdate><enddate>20070601</enddate><creator>Kuang, Shihuan</creator><creator>Kuroda, Kazuki</creator><creator>Le Grand, Fabien</creator><creator>Rudnicki, Michael A.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070601</creationdate><title>Asymmetric Self-Renewal and Commitment of Satellite Stem Cells in Muscle</title><author>Kuang, Shihuan ; Kuroda, Kazuki ; Le Grand, Fabien ; Rudnicki, Michael A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c550t-28e2796d9749bced65effea8b3ac9a20ed8bf69cc4826f8e0e5541c90fd348ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Cell Differentiation</topic><topic>Cell Separation</topic><topic>Cell Transplantation</topic><topic>Female</topic><topic>HUMDISEASE</topic><topic>Luminescent Proteins - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Muscle, Skeletal - cytology</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Myogenic Regulatory Factor 5 - metabolism</topic><topic>PAX7 Transcription Factor - metabolism</topic><topic>Receptors, Notch - metabolism</topic><topic>Satellite Cells, Skeletal Muscle - cytology</topic><topic>Satellite Cells, Skeletal Muscle - metabolism</topic><topic>STEMCELL</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuang, Shihuan</creatorcontrib><creatorcontrib>Kuroda, Kazuki</creatorcontrib><creatorcontrib>Le Grand, Fabien</creatorcontrib><creatorcontrib>Rudnicki, Michael A.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuang, Shihuan</au><au>Kuroda, Kazuki</au><au>Le Grand, Fabien</au><au>Rudnicki, Michael A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Asymmetric Self-Renewal and Commitment of Satellite Stem Cells in Muscle</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2007-06-01</date><risdate>2007</risdate><volume>129</volume><issue>5</issue><spage>999</spage><epage>1010</epage><pages>999-1010</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>Satellite cells play a central role in mediating the growth and regeneration of skeletal muscle. However, whether satellite cells are stem cells, committed progenitors, or dedifferentiated myoblasts has remained unclear. Using Myf5-Cre and ROSA26-YFP Cre-reporter alleles, we observed that in vivo 10% of sublaminar Pax7-expressing satellite cells have never expressed Myf5. Moreover, we found that Pax7+/Myf5− satellite cells gave rise to Pax7+/Myf5+ satellite cells through apical-basal oriented divisions that asymmetrically generated a basal Pax7+/Myf5− and an apical Pax7+/Myf5+ cells. Prospective isolation and transplantation into muscle revealed that whereas Pax7+/Myf5+ cells exhibited precocious differentiation, Pax7+/Myf5− cells extensively contributed to the satellite cell reservoir throughout the injected muscle. Therefore, we conclude that satellite cells are a heterogeneous population composed of stem cells and committed progenitors. 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subjects | Animals Cell Differentiation Cell Separation Cell Transplantation Female HUMDISEASE Luminescent Proteins - metabolism Male Mice Muscle, Skeletal - cytology Muscle, Skeletal - metabolism Myogenic Regulatory Factor 5 - metabolism PAX7 Transcription Factor - metabolism Receptors, Notch - metabolism Satellite Cells, Skeletal Muscle - cytology Satellite Cells, Skeletal Muscle - metabolism STEMCELL |
title | Asymmetric Self-Renewal and Commitment of Satellite Stem Cells in Muscle |
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