Odd skipped-related 1 identifies a population of embryonic fibro-adipogenic progenitors regulating myogenesis during limb development

Pedro Vallecillo-García, Mickael Orgeur, Sophie vom Hofe-Schneider, Jürgen Stumm, Verena Kappert, Daniel M. Ibrahim, Stefan T. Börno, Shinichiro Hayashi, Frédéric Relaix, Katrin Hildebrandt, Gerhard Sengle, Manuel Koch, Bernd Timmermann, Giovanna Marazzi, David A. Sassoon, Delphine Duprez and Sigmar Stricker ()
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Pedro Vallecillo-García: Freie Universität Berlin
Mickael Orgeur: Freie Universität Berlin
Sophie vom Hofe-Schneider: Freie Universität Berlin
Jürgen Stumm: Freie Universität Berlin
Verena Kappert: Freie Universität Berlin
Daniel M. Ibrahim: Max Planck Institute for Molecular Genetics
Stefan T. Börno: Max Planck Institute for Molecular Genetics
Shinichiro Hayashi: Inserm, IMRB U955-E10
Frédéric Relaix: Inserm, IMRB U955-E10
Katrin Hildebrandt: University of Cologne
Gerhard Sengle: University of Cologne
Manuel Koch: University of Cologne
Bernd Timmermann: Max Planck Institute for Molecular Genetics
Giovanna Marazzi: Stem Cells and Regenerative Medicine, ICAN-UMRS 1166, Université de Pierre et Marie Curie, Sorbonne Universités
David A. Sassoon: Stem Cells and Regenerative Medicine, ICAN-UMRS 1166, Université de Pierre et Marie Curie, Sorbonne Universités
Delphine Duprez: Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR7622, IBPS-Developmental Biology Laboratory
Sigmar Stricker: Freie Universität Berlin

Nature Communications, 2017, vol. 8, issue 1, 1-18

Abstract: Abstract Fibro-adipogenic progenitors (FAPs) are an interstitial cell population in adult skeletal muscle that support muscle regeneration. During development, interstitial muscle connective tissue (MCT) cells support proper muscle patterning, however the underlying molecular mechanisms are not well understood and it remains unclear whether adult FAPs and embryonic MCT cells share a common lineage. We show here that mouse embryonic limb MCT cells expressing the transcription factor Osr1, differentiate into fibrogenic and adipogenic cells in vivo and in vitro defining an embryonic FAP-like population. Genetic lineage tracing shows that developmental Osr1+ cells give rise to a subset of adult FAPs. Loss of Osr1 function leads to a reduction of myogenic progenitor proliferation and survival resulting in limb muscle patterning defects. Transcriptome and functional analyses reveal that Osr1+ cells provide a critical pro-myogenic niche via the production of MCT specific extracellular matrix components and secreted signaling factors.

Date: 2017
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DOI: 10.1038/s41467-017-01120-3

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