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

Nature Communications
Pedro Vallecillo-GarcíaSigmar Stricker

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.

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Citations

Feb 22, 2018·Skeletal Muscle·Osvaldo ContrerasEnrique Brandan
Dec 19, 2018·Annals of Plastic Surgery·Feng NiQingfeng Li
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Jun 24, 2021·Nature Communications·Joana Esteves de LimaDelphine Duprez

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Datasets Mentioned

BETA
GSE78056

Methods Mentioned

BETA
FACS
immunoprecipitation
PCR
ChIP
pulldown
RNA-Seq
acetylation
Electrophoresis
flow cytometry

Software Mentioned

FlowJo
Fluorender®
UCSC browser
DAVID
HTSeq
Amira®
DESeq2
GraphPad
iGenome
TopHat2

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