RT Journal Article
SR Electronic
T1 A switch in cilia-mediated Hedgehog signaling controls muscle stem cell quiescence and cell cycle progression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2019.12.21.884601
DO 10.1101/2019.12.21.884601
A1 Sara Betania Cruz-Migoni
A1 Kamalliawati Mohd Imran
A1 Aysha Wahid
A1 Oisharja Rahman
A1 James Briscoe
A1 Anne-Gaëlle Borycki
YR 2019
UL http://biorxiv.org/content/early/2019/12/22/2019.12.21.884601.abstract
AB Tissue homeostasis requires a tight control of stem cells to maintain quiescence in normal conditions, and ensure a balance between progenitor cell production and the need to preserve a stem cell pool in repair conditions. Using ex-vivo and in-vivo genetic approaches, we provide evidence that primary cilium-mediated repressive Hedgehog (Hh) signalling is required to maintain skeletal muscle stem cells (MuSCs) in a quiescent state. De-repression and further activation of Hh signalling initiates MuSC entry and progression through the cell cycle, and controls self-renewal to ensure efficient repair of injured muscles. We propose a model whereby disassembly of primary cilia upon MuSC activation induces a switch in Hh signalling from a repressive to active state that controls exit from quiescence. Positive Hh response in bi-potential muscle progenitor cells regulates also cell cycle progression and drives MuSC self-renewal. These findings identify Hh signalling as a major regulator of MuSC activity.HighlightsCilia-containing quiescent MuSCs are Hh signalling suppressedMuSC activation coincides with a switch to active Hh signallingSmo mutation delays cell cycle entry and progression, and causes impaired self-renewalPtch1 mutation promotes exit from quiescence, rapid cell cycle and increased self-renewal