Elsevier

Stem Cell Research

Volume 32, October 2018, Pages 8-16
Stem Cell Research

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

https://doi.org/10.1016/j.scr.2018.08.010Get rights and content
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Highlights

  • Odd skipped related 1 (Osr1) marks adult FAPs activated by acute injury

  • Osr1 is expressed in FAPs during phases of active myogenesis

  • Osr1 can be used to mark, access and lineage-trace adult injury-activated FAPs

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.

Keywords

Skeletal muscle
Fibro-adipogenic progenitors
Mesenchymal progenitors, Muscle interstitium
Muscle regeneration

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1

These authors contributed equally to this work.