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| Status |
Public on Dec 01, 2018 |
| Title |
Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Regeneration of skeletal muscle is dependent on the function of tissue-resident muscle stem cells (MuSC), known as satellite cells. MuSC dysfunction is central to muscle pathophysiology, including in age-associated loss of muscle regenerative capacity and congenital disorders such as Duchenne muscular dystrophy. Despite the central role of satellite cells in muscle regeneration, the signals controlling the balance between muscle stem cell quiescence, proliferation, and differentiation remain incompletely understood. Knowledge of the signals that maintain a quiescent state is particularly lacking, yet such cues are crucial to maintaining a stem cell reservoir that can meet the needs of regeneration throughout life. Here we identify Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, as a potent and essential trans-acting regulator of satellite cell quiescence. Key to this discovery is the development of a novel in vivo imaging-based screening strategy allowing identification of proteins that do not induce in vitro proliferation, but instead maintain MuSCs in a non-mitotic state, poised for rapid robust expansion upon transplantation. We demonstrate that OSM induces reversible exit from the cell cycle and induction of a global transcriptional program significantly enriched within a newly established satellite cell “quiescence signature”. Genetic ablation of the OSM receptor in mice demonstrates that signaling via OSM/R is essential for maintenance of satellite cell quiescence, and for proper skeletal muscle regeneration in vivo. Given that aberrant activation and exhaustion of stem cells is seen in a variety of disorders, OSM constitutes an attractive therapeutic target in muscle disease states.
Microarray profiling was used to directly test the hypothesis that OSMR signaling in muscle stem cells promotes their engraftment by inducing a global transcriptional state equivalent to that of quiescent, freshly isolated, non-activated MuSC.
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| Overall design |
Comparison of Oncostatin M-treated cultured muscle stem cells with either fresh or cultured but non-Oncostatin M-treated muscle stem cells
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| Contributor(s) |
Sampath SC, Sampath SC, Ho A, Corbel SY, Millstone J, Lamb J, Walker JR, Kinzel B, Schmedt C, Blau HM |
| Citation(s) |
29670077 |
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| Submission date |
Jun 18, 2015 |
| Last update date |
Feb 11, 2019 |
| Contact name |
John R Walker |
| E-mail(s) |
[email protected]
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| Phone |
858-812-1636
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| Organization name |
Genomics Institute of the Novartis Research Foundation
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| Lab |
Genetics Core
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| Street address |
10675 John Jay Hopkins
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| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92121 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (3) |
| GSM1714720 |
Freshly isolated muscle stem cells |
| GSM1714724 |
Muscle stem cells cultured in 10% FBS for 3 days |
| GSM1714725 |
Muscle stem cells cultured in 10% FBS and 100 ng/mL oncostatin M for 3 days |
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| Relations |
| BioProject |
PRJNA287320 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE69976_RAW.tar |
10.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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