Sara Ancel, Joris Michaud, Federico Sizzano, Loic Tauzin, Manuel Oliveira, Eugenia Migliavacca, Svenja C Schüler, Sruthi Raja, Gabriele Dammone, Sonia Karaz, José L Sánchez-García, Sylviane Metairon, Guillaume Jacot, C Florian Bentzinger, Jérôme N Feige, Pascal Stuelsatz
{"title":"双色 PAX7 和 MYF5 体内报告器,用于研究再生和衰老过程中肌肉干细胞的异质性。","authors":"Sara Ancel, Joris Michaud, Federico Sizzano, Loic Tauzin, Manuel Oliveira, Eugenia Migliavacca, Svenja C Schüler, Sruthi Raja, Gabriele Dammone, Sonia Karaz, José L Sánchez-García, Sylviane Metairon, Guillaume Jacot, C Florian Bentzinger, Jérôme N Feige, Pascal Stuelsatz","doi":"10.1016/j.stemcr.2024.05.005","DOIUrl":null,"url":null,"abstract":"<p><p>Increasing evidence suggests that the muscle stem cell (MuSC) pool is heterogeneous. In particular, a rare subset of PAX7-positive MuSCs that has never expressed the myogenic regulatory factor MYF5 displays unique self-renewal and engraftment characteristics. However, the scarcity and limited availability of protein markers make the characterization of these cells challenging. Here, we describe the generation of StemRep reporter mice enabling the monitoring of PAX7 and MYF5 proteins based on equimolar levels of dual nuclear fluorescence. High levels of PAX7 protein and low levels of MYF5 delineate a deeply quiescent MuSC subpopulation with an increased capacity for asymmetric division and distinct dynamics of activation, proliferation, and commitment. Aging primarily reduces the MYF5<sup>Low</sup> MuSCs and skews the stem cell pool toward MYF5<sup>High</sup> cells with lower quiescence and self-renewal potential. Altogether, we establish the StemRep model as a versatile tool to study MuSC heterogeneity and broaden our understanding of mechanisms regulating MuSC quiescence and self-renewal in homeostatic, regenerating, and aged muscles.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1024-1040"},"PeriodicalIF":5.9000,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252486/pdf/","citationCount":"0","resultStr":"{\"title\":\"A dual-color PAX7 and MYF5 in vivo reporter to investigate muscle stem cell heterogeneity in regeneration and aging.\",\"authors\":\"Sara Ancel, Joris Michaud, Federico Sizzano, Loic Tauzin, Manuel Oliveira, Eugenia Migliavacca, Svenja C Schüler, Sruthi Raja, Gabriele Dammone, Sonia Karaz, José L Sánchez-García, Sylviane Metairon, Guillaume Jacot, C Florian Bentzinger, Jérôme N Feige, Pascal Stuelsatz\",\"doi\":\"10.1016/j.stemcr.2024.05.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Increasing evidence suggests that the muscle stem cell (MuSC) pool is heterogeneous. In particular, a rare subset of PAX7-positive MuSCs that has never expressed the myogenic regulatory factor MYF5 displays unique self-renewal and engraftment characteristics. However, the scarcity and limited availability of protein markers make the characterization of these cells challenging. Here, we describe the generation of StemRep reporter mice enabling the monitoring of PAX7 and MYF5 proteins based on equimolar levels of dual nuclear fluorescence. High levels of PAX7 protein and low levels of MYF5 delineate a deeply quiescent MuSC subpopulation with an increased capacity for asymmetric division and distinct dynamics of activation, proliferation, and commitment. Aging primarily reduces the MYF5<sup>Low</sup> MuSCs and skews the stem cell pool toward MYF5<sup>High</sup> cells with lower quiescence and self-renewal potential. Altogether, we establish the StemRep model as a versatile tool to study MuSC heterogeneity and broaden our understanding of mechanisms regulating MuSC quiescence and self-renewal in homeostatic, regenerating, and aged muscles.</p>\",\"PeriodicalId\":21885,\"journal\":{\"name\":\"Stem Cell Reports\",\"volume\":\" \",\"pages\":\"1024-1040\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-07-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252486/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stem Cell Reports\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.stemcr.2024.05.005\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cell Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stemcr.2024.05.005","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/13 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
A dual-color PAX7 and MYF5 in vivo reporter to investigate muscle stem cell heterogeneity in regeneration and aging.
Increasing evidence suggests that the muscle stem cell (MuSC) pool is heterogeneous. In particular, a rare subset of PAX7-positive MuSCs that has never expressed the myogenic regulatory factor MYF5 displays unique self-renewal and engraftment characteristics. However, the scarcity and limited availability of protein markers make the characterization of these cells challenging. Here, we describe the generation of StemRep reporter mice enabling the monitoring of PAX7 and MYF5 proteins based on equimolar levels of dual nuclear fluorescence. High levels of PAX7 protein and low levels of MYF5 delineate a deeply quiescent MuSC subpopulation with an increased capacity for asymmetric division and distinct dynamics of activation, proliferation, and commitment. Aging primarily reduces the MYF5Low MuSCs and skews the stem cell pool toward MYF5High cells with lower quiescence and self-renewal potential. Altogether, we establish the StemRep model as a versatile tool to study MuSC heterogeneity and broaden our understanding of mechanisms regulating MuSC quiescence and self-renewal in homeostatic, regenerating, and aged muscles.
期刊介绍:
Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.