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

Pedro Vallecillo-García (1, 2) , Mickael Orgeur (1, 2, 3) , Sophie vom Hofe-Schneider (1) , Jürgen Stumm (1) , Verena Kappert (1, 2) , Daniel M. Ibrahim (2) , Stefan T. Börno (2) , Shinichiro Hayashi (4, 5) , Frédéric Relaix (6, 5) , Katrin Hildebrandt (7) , Gerhard Sengle (7) , Manuel Koch (7) , Bernd Timmermann (2) , Giovanna Marazzi (8, 9) , David A. Sassoon (8) , Delphine Duprez (3) , Sigmar Stricker (1, 2)

1 Freie Universität Berlin
2 MPIMG - Max Planck Institute for Molecular Genetics
3 LBD - Laboratoire de Biologie du Développement [IBPS]
4 Inserm U955 - Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18)
5 UPEC Médecine - Université Paris-Est Créteil Val-de-Marne - Faculté de médecine
6 IMRB - Institut Mondor de Recherche Biomédicale
7 Universität zu Köln = University of Cologne
8 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
9 IHU ICAN - Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière]

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.

Domaines: Sciences du Vivant [q-bio]

Pedro Vallecillo-García, Mickael Orgeur, Sophie vom Hofe-Schneider, Jürgen Stumm, Verena Kappert, et al.. Odd skipped-related 1 identifies a population of embryonic fibro-adipogenic progenitors regulating myogenesis during limb development. Nature Communications, 2017, 8, pp.1218. ⟨10.1038/s41467-017-01120-3⟩. ⟨hal-02386394⟩