Single-cell RNA-seq - Jmj KO, Utx KO, Tdt.Control

Stem cells reside in specialized niches that play a critical role in modulating their fate. It remains unknown how MuSC adapt to the modified milieu to mediate muscle repair. Here, we show that the epigenetic enzyme JMJD3 coordinates MuSC adaptation to the regenerative niche in a non-cell autonomous manner where it modifies their extracellular matrix to integrate signaling that stimulates exit of quiescence. Genomics and transcriptomics approaches identified the hyaluronic acid (HA) synthesis enzyme Has2 as a key JMJD3 target gene that allows MuSCs to integrate signals from the regenerative niche. Overall design: Single-cell RNA-Seq was performed on muscle satellite cells prepared from indicated mouse strains. Muscle satellite cells were isolated by FACS at 40 h post Cardiotoxin injury.