Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M.

Autor: Sampath SC; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA. ssampath@gnf.org.; Genomics Institute of the Novartis Research Foundation, San Diego, CA, 92121, USA. ssampath@gnf.org.; Division of Musculoskeletal Imaging, Department of Radiology, University of California San Diego School of Medicine, San Diego, CA, 92103, USA. ssampath@gnf.org., Sampath SC; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.; Genomics Institute of the Novartis Research Foundation, San Diego, CA, 92121, USA.; Division of Musculoskeletal Imaging, Department of Radiology, University of California San Diego School of Medicine, San Diego, CA, 92103, USA., Ho ATV; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA., Corbel SY; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.; Genomics Institute of the Novartis Research Foundation, San Diego, CA, 92121, USA., Millstone JD; Genomics Institute of the Novartis Research Foundation, San Diego, CA, 92121, USA., Lamb J; Genomics Institute of the Novartis Research Foundation, San Diego, CA, 92121, USA., Walker J; Genomics Institute of the Novartis Research Foundation, San Diego, CA, 92121, USA., Kinzel B; Novartis Institutes for BioMedical Research, 4056, Basel, Switzerland., Schmedt C; Genomics Institute of the Novartis Research Foundation, San Diego, CA, 92121, USA., Blau HM; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA. hblau@stanford.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 Apr 18; Vol. 9 (1), pp. 1531. Date of Electronic Publication: 2018 Apr 18.
DOI: 10.1038/s41467-018-03876-8
Abstrakt: 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.
Databáze: MEDLINE