Jmjd3-Lab UTX-Lab CUT&Tag

Stem cells reside in specialized niches that play a critical role in modulating their fate. Supporting cells in the niche instruct fate changes to the stem cells through epigenetic enzymes that transduce cell signaling to modify gene expression. Recent studies showed that the innate immune response to muscle injury alters the muscle stem cell (MuSC) niche, 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, we identified a specific role for JMJD3 in regulating the expression of genes that allow MuSCs to adapt to the modified niche of regenerating muscle. We aim to determine the differential occupancy of histone H3 lysine 4 trimethyl mark muscle satellite stem cells isolated from JMJD3scKO, UTXscKO and Wild-type mice. Overall design: CUT&Tag was performed on muscle satellite cells isolated from hindlimb muscles at 30 hrs post cardiotoxin injury.