APC is required for muscle stem cell proliferation and skeletal muscle tissue repair
The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant...
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Veröffentlicht in: | The Journal of cell biology 2015-08, Vol.210 (5), p.717-726 |
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description | The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues. |
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In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.201501053</identifier><identifier>PMID: 26304725</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Adenomatous Polyposis Coli Protein - genetics ; Adenomatous Polyposis Coli Protein - physiology ; Adult Stem Cells - cytology ; Adult Stem Cells - physiology ; Animals ; Apoptosis - genetics ; beta Catenin - metabolism ; Cell cycle ; Cell Cycle - genetics ; Cell Differentiation - genetics ; Cell Differentiation - physiology ; Cell Proliferation ; Cell Survival - genetics ; DNA repair ; Female ; Male ; Mice ; Mice, Transgenic ; Muscle Development - genetics ; Muscle Development - physiology ; Muscle, Skeletal - cytology ; Muscle, Skeletal - physiology ; Musculoskeletal system ; Regeneration - genetics ; Regeneration - physiology ; RNA Interference ; RNA, Small Interfering - genetics ; Satellite Cells, Skeletal Muscle - cytology ; Satellite Cells, Skeletal Muscle - physiology ; Signal transduction ; Stem cells ; Tissues ; Wnt Proteins - metabolism ; Wnt Signaling Pathway - genetics ; Wound Healing - genetics</subject><ispartof>The Journal of cell biology, 2015-08, Vol.210 (5), p.717-726</ispartof><rights>2015 Parisi et al.</rights><rights>Copyright Rockefeller University Press Aug 31, 2015</rights><rights>2015 Parisi et al. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-22e2d22f9b7c9e57ac04e545f8f83f417872571ee28882fa0c9d3ee7fcb559fb3</citedby><cites>FETCH-LOGICAL-c481t-22e2d22f9b7c9e57ac04e545f8f83f417872571ee28882fa0c9d3ee7fcb559fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26304725$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Parisi, Alice</creatorcontrib><creatorcontrib>Lacour, Floriane</creatorcontrib><creatorcontrib>Giordani, Lorenzo</creatorcontrib><creatorcontrib>Colnot, Sabine</creatorcontrib><creatorcontrib>Maire, Pascal</creatorcontrib><creatorcontrib>Le Grand, Fabien</creatorcontrib><title>APC is required for muscle stem cell proliferation and skeletal muscle tissue repair</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues.</description><subject>Adenomatous Polyposis Coli Protein - genetics</subject><subject>Adenomatous Polyposis Coli Protein - physiology</subject><subject>Adult Stem Cells - cytology</subject><subject>Adult Stem Cells - physiology</subject><subject>Animals</subject><subject>Apoptosis - genetics</subject><subject>beta Catenin - metabolism</subject><subject>Cell cycle</subject><subject>Cell Cycle - genetics</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Proliferation</subject><subject>Cell Survival - genetics</subject><subject>DNA repair</subject><subject>Female</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Muscle Development - genetics</subject><subject>Muscle Development - physiology</subject><subject>Muscle, Skeletal - cytology</subject><subject>Muscle, Skeletal - physiology</subject><subject>Musculoskeletal system</subject><subject>Regeneration - genetics</subject><subject>Regeneration - physiology</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - genetics</subject><subject>Satellite Cells, Skeletal Muscle - cytology</subject><subject>Satellite Cells, Skeletal Muscle - physiology</subject><subject>Signal transduction</subject><subject>Stem cells</subject><subject>Tissues</subject><subject>Wnt Proteins - metabolism</subject><subject>Wnt Signaling Pathway - genetics</subject><subject>Wound Healing - genetics</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUFrGzEQRkVJqZ2kx1yLIJdcNhlpJa_2UjCmSQqG9OCchVY7auTurmxpt9B_H4XEpslpBubxMR-PkAsG1wxUebO1zTUHJoGBLD-ROZMCCsUEnJA5AGdFLbmckdOUtgAgKlF-ITO-KPPK5Zxslr9W1CcacT_5iC11IdJ-SrZDmkbsqcWuo7sYOu8wmtGHgZqhpekPdjia7sCOPqUJc8zO-HhOPjvTJfz6Ns_I4-2Pzeq-WD_c_Vwt14UVio0F58hbzl3dVLZGWRkLAqWQTjlVOsEqlV-sGCJXSnFnwNZtiVg520hZu6Y8I99fc3dT02NrcRij6fQu-t7EfzoYr99fBv-kf4e_WkgpFec54OotIIb9hGnUvU8vjc2AYUqaVaBqELCQGb38gG7DFIdcL1MMFgslADJVvFI2hpQiuuMzDPSLL5196aOvzH_7v8GRPggqnwFNFJGA</recordid><startdate>20150831</startdate><enddate>20150831</enddate><creator>Parisi, Alice</creator><creator>Lacour, Floriane</creator><creator>Giordani, Lorenzo</creator><creator>Colnot, Sabine</creator><creator>Maire, Pascal</creator><creator>Le Grand, Fabien</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</general><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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150831</creationdate><title>APC is required for muscle stem cell proliferation and skeletal muscle tissue repair</title><author>Parisi, Alice ; Lacour, Floriane ; Giordani, Lorenzo ; Colnot, Sabine ; Maire, Pascal ; Le Grand, Fabien</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-22e2d22f9b7c9e57ac04e545f8f83f417872571ee28882fa0c9d3ee7fcb559fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adenomatous Polyposis Coli Protein - genetics</topic><topic>Adenomatous Polyposis Coli Protein - physiology</topic><topic>Adult Stem Cells - cytology</topic><topic>Adult Stem Cells - physiology</topic><topic>Animals</topic><topic>Apoptosis - genetics</topic><topic>beta Catenin - metabolism</topic><topic>Cell cycle</topic><topic>Cell Cycle - genetics</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - physiology</topic><topic>Cell Proliferation</topic><topic>Cell Survival - genetics</topic><topic>DNA repair</topic><topic>Female</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Muscle Development - genetics</topic><topic>Muscle Development - physiology</topic><topic>Muscle, Skeletal - cytology</topic><topic>Muscle, Skeletal - physiology</topic><topic>Musculoskeletal system</topic><topic>Regeneration - genetics</topic><topic>Regeneration - physiology</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - genetics</topic><topic>Satellite Cells, Skeletal Muscle - cytology</topic><topic>Satellite Cells, Skeletal Muscle - physiology</topic><topic>Signal transduction</topic><topic>Stem cells</topic><topic>Tissues</topic><topic>Wnt Proteins - metabolism</topic><topic>Wnt Signaling Pathway - genetics</topic><topic>Wound Healing - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Parisi, Alice</creatorcontrib><creatorcontrib>Lacour, Floriane</creatorcontrib><creatorcontrib>Giordani, Lorenzo</creatorcontrib><creatorcontrib>Colnot, Sabine</creatorcontrib><creatorcontrib>Maire, Pascal</creatorcontrib><creatorcontrib>Le Grand, Fabien</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Parisi, Alice</au><au>Lacour, Floriane</au><au>Giordani, Lorenzo</au><au>Colnot, Sabine</au><au>Maire, Pascal</au><au>Le Grand, Fabien</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>APC is required for muscle stem cell proliferation and skeletal muscle tissue repair</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2015-08-31</date><risdate>2015</risdate><volume>210</volume><issue>5</issue><spage>717</spage><epage>726</epage><pages>717-726</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><coden>JCLBA3</coden><abstract>The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>26304725</pmid><doi>10.1083/jcb.201501053</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenomatous Polyposis Coli Protein - genetics Adenomatous Polyposis Coli Protein - physiology Adult Stem Cells - cytology Adult Stem Cells - physiology Animals Apoptosis - genetics beta Catenin - metabolism Cell cycle Cell Cycle - genetics Cell Differentiation - genetics Cell Differentiation - physiology Cell Proliferation Cell Survival - genetics DNA repair Female Male Mice Mice, Transgenic Muscle Development - genetics Muscle Development - physiology Muscle, Skeletal - cytology Muscle, Skeletal - physiology Musculoskeletal system Regeneration - genetics Regeneration - physiology RNA Interference RNA, Small Interfering - genetics Satellite Cells, Skeletal Muscle - cytology Satellite Cells, Skeletal Muscle - physiology Signal transduction Stem cells Tissues Wnt Proteins - metabolism Wnt Signaling Pathway - genetics Wound Healing - genetics |
title | APC is required for muscle stem cell proliferation and skeletal muscle tissue repair |
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