Tissue-Specific Stem Cells

Notch Signaling Is Necessary to Maintain Quiescence in Adult Muscle Stem Cells†‡§

  1. Christopher R.R. Bjornson1,2,
  2. Tom H. Cheung1,2,
  3. Ling Liu1,2,
  4. Pinky V. Tripathi1,2,
  5. Katherine M. Steeper1,2,
  6. Thomas A. Rando1,2,3,¶,*

Article first published online: 18 JAN 2012

DOI: 10.1002/stem.773

Issue

STEM CELLS

STEM CELLS

Volume 30, Issue 2, pages 232–242, February 2012

Additional Information

How to Cite

Bjornson, C. R.R., Cheung, T. H., Liu, L., Tripathi, P. V., Steeper, K. M. and Rando, T. A. (2012), Notch Signaling Is Necessary to Maintain Quiescence in Adult Muscle Stem Cells. STEM CELLS, 30: 232–242. doi: 10.1002/stem.773

Author Information

  1. 1

    Department of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA

  2. 2

    The Glenn Laboratories for the Biology of Aging, Stanford University, Stanford, California, USA

  3. 3

    Neurology Service, VA Palo Alto Health Care System, Palo Alto, California, USA

  1. Telephone: 650-849-1999; Fax: 650-858-3935

*The Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine, Stanford, CA 94305-5235, USA

  1. †

    Author contributions: C.R.R.B.: project conception and design, data collection, data analysis and interpretation, and manuscript writing; T.H.C. and L.L.: experiment design and data collection, analysis, and interpretation; P.V.T. and K.M.S.: technical assistance and data collection and assembly; T.A.R.: project conception and design, data analysis and interpretation, manuscript writing, and financial support.

  2. ‡

    Disclosure of potential conflicts of interest is found at the end of this article.

  3. §

    First published online in STEM CELLSEXPRESS November 1, 2011.

Publication History

  1. Issue published online: 18 JAN 2012
  2. Article first published online: 18 JAN 2012
  3. Accepted manuscript online: 1 NOV 2011 02:20PM EST
  4. Manuscript Accepted: 12 OCT 2011
  5. Manuscript Received: 12 MAY 2011

Funded by

  • Glenn Foundation for Medical Research and by grants from the NIH. Grant Numbers: P01 AG036695, R37 AG23806, R01 AR056849
  • NIH Director's Pioneer Award) and the Department of Veterans Affairs (Merit Review)

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Keywords:

  • Notch;
  • RBP-J;
  • Satellite Cell;
  • Quiescence

Abstract

Satellite cells (SCs) are myogenic stem cells found in skeletal muscle that function to repair tissue damaged by injury or disease. SCs are quiescent at rest, although the signaling pathways required to maintain quiescence are unknown. Using a transgenic Notch reporter mouse and quantitative reverse-transcription polymerase chain reaction analysis of Notch target genes, we determined that Notch signaling is active in quiescent SCs. SC-specific deletion of recombining binding protein-Jκ (RBP-Jκ), a nuclear factor required for Notch signaling, resulted in the depletion of the SC pool and muscles that lacked any ability to regenerate in response to injury. SC depletion was not due to apoptosis. Rather, RBP-Jκ-deficient SCs spontaneously activate, fail to self-renew, and undergo terminal differentiation. Intriguingly, most of the cells differentiate without first dividing. They then fuse with adjacent myofibers, leading to the gradual disappearance of SCs from the muscle. These results demonstrate the requirement of Notch signaling for the maintenance of the quiescent state and for muscle stem cell homeostasis by the regulation of self-renewal and differentiation, processes that are all critical for normal postnatal myogenesis. STEM CELLS 2012; 30:232–242.

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