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

Stem Cell Research
Jürgen StummSigmar Stricker

Abstract

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.

Citations

Jun 27, 2019·Life Science Alliance·Milica MarinkovicGianni Cesareni
Dec 23, 2019·Journal of Cell Communication and Signaling·Osvaldo Contreras
Feb 13, 2020·Frontiers in Cell and Developmental Biology·Nicolas CollaoMichael De Lisio
Oct 16, 2019·Frontiers in Physiology·Alessandro PalmaGianni Cesareni
Oct 5, 2019·Animal : an International Journal of Animal Bioscience·X LiM Du
Jul 9, 2020·Veterinary Pathology·Peter VogelDavid R Powell
Oct 21, 2020·Journal of Cachexia, Sarcopenia and Muscle·Xiaoyan WeiSigmar Stricker
Jun 11, 2020·Seminars in Cell & Developmental Biology·Françoise Helmbacher, Sigmar Stricker
Jun 5, 2021·Scientific Reports·Ariel WaismanDaniel Kopinke

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