Odd skipped-related 1 (Osr1) identifies muscle-interstitial fibro-adipogenic progenitors (FAPs) activated by acute injury - ScienceDirect

Stem Cell Research

David Ollitrault^2,3¹  Sophie Vom Hofe-Schneider^1²  Jürgen Stumm^1³  Heinrich Schrewe^4⁴  Pedro Vallecillo-García^1⁵ 

[1] Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany^4;ICAN, Institute of Cardiometabolism and Nutrition, 75013 Paris, France^3;Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany^1;Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA^5;Stem Cells and Regenerative Medicine, ICAN-UMRS 1166, Université de Pierre et Marie Curie, Sorbonne Universités, 75013 Paris, France^2

关键词: Skeletal muscle;    Fibro-adipogenic progenitors;    Mesenchymal progenitors, Muscle interstitium;    Muscle regeneration;   

DOI  :  10.1016/j.scr.2018.08.010

学科分类：生物科学（综合）

来源: Elsevier

【 摘 要 】

Fibro-adipogenic progenitors (FAPs) are resident mesenchymal progenitors in adult skeletal muscle that support muscle repair, but also give rise to fibrous and adipose infiltration in response to disease and chronic injury. FAPs are identified using cell surface markers that do not distinguish between quiescent FAPs and FAPs actively engaged in the regenerative process. We have shown previously that FAPs are derived from cells that express the transcription factor Osr1 during development. Here we show that adult FAPs express Osr1 at low levels and frequency, however upon acute injury FAPs reactivate Osr1 expression in the injured tissue. Osr1+ FAPs are enriched in proliferating and apoptotic cells demonstrating that Osr1 identifies activated FAPs. In vivo genetic lineage tracing shows that Osr1+ activated FAPs return to the resident FAP pool after regeneration as well as contribute to adipocytes after glycerol-induced fatty degeneration. In conclusion, reporter LacZ or eGFP-CreERt2 expression from the endogenous Osr1 locus serves as marker for FACS isolation and tamoxifen-induced manipulation of activated FAPs.

【 授权许可】

Unknown