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

Srinath C. Sampath, Srihari C. Sampath, Andrew T.V. Ho, Stéphane Y. Corbel, Joshua D. Millstone, John Lamb, John Walker, Bernd Kinzel, Christian Schmedt, Helen M. Blau
doi: https://doi.org/10.1101/303586
Srinath C. Sampath
1Baxter 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
2Genomics Institute of the Novartis Research Foundation, San Diego CA 92121, USA
4Division of Musculoskeletal Imaging, Department of Radiology, University of California San Diego School of Medicine, San Diego CA 92103, USA
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Srihari C. Sampath
1Baxter 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
2Genomics Institute of the Novartis Research Foundation, San Diego CA 92121, USA
4Division of Musculoskeletal Imaging, Department of Radiology, University of California San Diego School of Medicine, San Diego CA 92103, USA
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Andrew T.V. Ho
1Baxter 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
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Stéphane Y. Corbel
1Baxter 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
2Genomics Institute of the Novartis Research Foundation, San Diego CA 92121, USA
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Joshua D. Millstone
2Genomics Institute of the Novartis Research Foundation, San Diego CA 92121, USA
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John Lamb
2Genomics Institute of the Novartis Research Foundation, San Diego CA 92121, USA
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John Walker
2Genomics Institute of the Novartis Research Foundation, San Diego CA 92121, USA
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Bernd Kinzel
3Novartis Institutes for BioMedical Research, 4056 Basel, Switzerland
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Christian Schmedt
2Genomics Institute of the Novartis Research Foundation, San Diego CA 92121, USA
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Helen M. Blau
1Baxter 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
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Abstract

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.

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Posted April 18, 2018.
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Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M
Srinath C. Sampath, Srihari C. Sampath, Andrew T.V. Ho, Stéphane Y. Corbel, Joshua D. Millstone, John Lamb, John Walker, Bernd Kinzel, Christian Schmedt, Helen M. Blau
bioRxiv 303586; doi: https://doi.org/10.1101/303586
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Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M
Srinath C. Sampath, Srihari C. Sampath, Andrew T.V. Ho, Stéphane Y. Corbel, Joshua D. Millstone, John Lamb, John Walker, Bernd Kinzel, Christian Schmedt, Helen M. Blau
bioRxiv 303586; doi: https://doi.org/10.1101/303586

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