Polycomb Ezh1 maintains murine muscle stem cell quiescence through non-canonical regulation of Notch signaling

Xuesong Feng; A Hongjun Wang; Aster H Juan; Kyung Dae Ko; Kan Jiang; Giulia Riparini; Veronica Ciuffoli; Aissah Kaba; Christopher Lopez; Faiza Naz; Michal Jarnik; Elizabeth Aliberti; Shenyuan Hu; Jessica Segalés; Mamduh Khateb; Natalia Acevedo-Luna; Davide Randazzo; Tom H Cheung; Pura Muñoz-Cánoves; Stefania Dell'Orso; Vittorio Sartorelli

doi:10.1016/j.devcel.2023.04.005

Polycomb Ezh1 maintains murine muscle stem cell quiescence through non-canonical regulation of Notch signaling

Dev Cell. 2023 Jun 19;58(12):1052-1070.e10. doi: 10.1016/j.devcel.2023.04.005. Epub 2023 Apr 26.

Authors

Xuesong Feng¹, A Hongjun Wang¹, Aster H Juan¹, Kyung Dae Ko¹, Kan Jiang², Giulia Riparini¹, Veronica Ciuffoli¹, Aissah Kaba¹, Christopher Lopez¹, Faiza Naz³, Michal Jarnik⁴, Elizabeth Aliberti¹, Shenyuan Hu⁵, Jessica Segalés⁶, Mamduh Khateb¹, Natalia Acevedo-Luna¹, Davide Randazzo⁷, Tom H Cheung⁵, Pura Muñoz-Cánoves⁸, Stefania Dell'Orso³, Vittorio Sartorelli⁹

Affiliations

¹ Laboratory of Muscle Stem Cells & Gene Regulation, NIAMS, NIH, Bethesda, MD, USA.
² Biodata Mining & Discovery Section, NIAMS, NIH, Bethesda, MD, USA.
³ Genomic Technology Section, NIAMS, NIH, Bethesda, MD, USA.
⁴ Cell Biology and Neurobiology Branch, NICHD, NIH, Bethesda, MD, USA.
⁵ Division of Life Sciences, State Key Laboratory of Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Hong Kong, China.
⁶ Department of Medicine and Life Sciences (MELIS), Pompeu Fabra University (UPF), Barcelona, Spain.
⁷ Light Imaging Section, NIAMS, NIH, Bethesda, MD, USA.
⁸ Department of Medicine and Life Sciences (MELIS), Pompeu Fabra University (UPF), Barcelona, Spain; Altos Labs Inc, San Diego, CA, USA.
⁹ Laboratory of Muscle Stem Cells & Gene Regulation, NIAMS, NIH, Bethesda, MD, USA. Electronic address: vittorio.sartorelli@nih.gov.

PMID: 37105173
PMCID: PMC10330238 (available on 2024-06-19)
DOI: 10.1016/j.devcel.2023.04.005

Abstract

Organismal homeostasis and regeneration are predicated on committed stem cells that can reside for long periods in a mitotically dormant but reversible cell-cycle arrest state defined as quiescence. Premature escape from quiescence is detrimental, as it results in stem cell depletion, with consequent defective tissue homeostasis and regeneration. Here, we report that Polycomb Ezh1 confers quiescence to murine muscle stem cells (MuSCs) through a non-canonical function. In the absence of Ezh1, MuSCs spontaneously exit quiescence. Following repeated injuries, the MuSC pool is progressively depleted, resulting in failure to sustain proper muscle regeneration. Rather than regulating repressive histone H3K27 methylation, Ezh1 maintains gene expression of the Notch signaling pathway in MuSCs. Selective genetic reconstitution of the Notch signaling corrects stem cell number and re-establishes quiescence of Ezh1^-/- MuSCs.

Keywords: Ezh1; Notch signaling; Polycomb; cilia; epigenetics; muscle regeneration; muscle stem cells.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Animals
Cell Cycle Checkpoints
Cell Division
Mice
Muscles
Signal Transduction*
Stem Cells*

Abstract

Publication types

MeSH terms

Grants and funding