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bioRxiv · 10.1101/2019.12.21.884601

A switch in cilia-mediated Hedgehog signaling controls muscle stem cell quiescence and cell cycle progression

Cruz-Migoni, S. B.·Mohd Imran, K.·Wahid, A.·Rahman, O.·Briscoe, J.·Borycki, A.-G.
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Abstract

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. HighlightsO_LICilia-containing quiescent MuSCs are Hh signalling suppressed C_LIO_LIMuSC activation coincides with a switch to active Hh signalling C_LIO_LISmo mutation delays cell cycle entry and progression, and causes impaired self-renewal C_LIO_LIPtch1 mutation promotes exit from quiescence, rapid cell cycle and increased self-renewal C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=147 HEIGHT=200 SRC="FIGDIR/small/884601v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1cbaa81org.highwire.dtl.DTLVardef@273898org.highwire.dtl.DTLVardef@f4b26corg.highwire.dtl.DTLVardef@edda2c_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Cruz-Migoni, S. B., Mohd Imran, K., Wahid, A., Rahman, O., Briscoe, J., Borycki, A.-G.. 2019-12-22. A switch in cilia-mediated Hedgehog signaling controls muscle stem cell quiescence and cell cycle progression. https://doi.org/10.1101/2019.12.21.884601

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