RT Journal Article
SR Electronic
T1 Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 303586
DO 10.1101/303586
A1 Sampath, Srinath C.
A1 Sampath, Srihari C.
A1 Ho, Andrew T.V.
A1 Corbel, Stéphane Y.
A1 Millstone, Joshua D.
A1 Lamb, John
A1 Walker, John
A1 Kinzel, Bernd
A1 Schmedt, Christian
A1 Blau, Helen M.
YR 2018
UL http://biorxiv.org/content/early/2018/04/18/303586.abstract
AB The balance between stem cell quiescence and proliferation in skeletal muscle is tightly controlled, but perturbed in a variety of disease states. Despite progress in identifying activators of stem cell proliferation, the niche factor(s) responsible for quiescence induction remain unclear. Here we report an in vivo imaging-based screen which identifies Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, as a potent inducer of muscle stem cell (MuSC, satellite cell) quiescence. OSM is produced by muscle fibers, induces reversible MuSC cell cycle exit, and maintains stem cell regenerative capacity as judged by serial transplantation. Conditional OSM receptor deletion in satellite cells leads to stem cell depletion and impaired regeneration following injury. These results identify Oncostatin M as a secreted niche factor responsible for quiescence induction, and for the first time establish a direct connection between induction of quiescence, stemness, and transplantation potential in solid organ stem cells.