Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state.

Publication ,  Journal Article
Chakkalakal, JV; Christensen, J; Xiang, W; Tierney, MT; Boscolo, FS; Sacco, A; Brack, AS
Published in: Development
April 2014

Across different niches, subsets of highly functional stem cells are maintained in a relatively dormant rather than proliferative state. Our understanding of proliferative dynamics in tissue-specific stem cells during conditions of increased tissue turnover remains limited. Using a TetO-H2B-GFP reporter of proliferative history, we identify skeletal muscle stem cell, or satellite cells, that retain (LRC) or lose (nonLRC) the H2B-GFP label. We show in mice that LRCs and nonLRCs are formed at birth and persist during postnatal growth and adult muscle repair. Functionally, LRCs and nonLRCs are born equivalent and transition during postnatal maturation into distinct and hierarchically organized subsets. Adult LRCs give rise to LRCs and nonLRCs; the former are able to self-renew, whereas the latter are restricted to differentiation. Expression analysis revealed the CIP/KIP family members p21(cip1) (Cdkn1a) and p27(kip1) (Cdkn1b) to be expressed at higher levels in LRCs. In accordance with a crucial role in LRC fate, loss of p27(kip1) promoted proliferation and differentiation of LRCs in vitro and impaired satellite cell self-renewal after muscle injury. By contrast, loss of p21(cip1) only affected nonLRCs, in which myogenic commitment was inhibited. Our results provide evidence that restriction of self-renewal potential to LRCs is established early in life and is maintained during increased tissue turnover through the cell cycle inhibitor p27(kip1). They also reveal the differential role of CIP/KIP family members at discrete steps within the stem cell hierarchy.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Development

DOI

EISSN

1477-9129

Publication Date

April 2014

Volume

141

Issue

8

Start / End Page

1649 / 1659

Location

England

Related Subject Headings

  • Stem Cells
  • Staining and Labeling
  • Phenotype
  • Muscular Dystrophy, Animal
  • Muscle, Skeletal
  • Mice, Inbred mdx
  • Mice, Inbred C57BL
  • Mice
  • Histones
  • Green Fluorescent Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chakkalakal, J. V., Christensen, J., Xiang, W., Tierney, M. T., Boscolo, F. S., Sacco, A., & Brack, A. S. (2014). Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state. Development, 141(8), 1649–1659. https://doi.org/10.1242/dev.100842
Chakkalakal, Joe V., Josef Christensen, Wanyi Xiang, Mathew T. Tierney, Francesca S. Boscolo, Alessandra Sacco, and Andrew S. Brack. “Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state.Development 141, no. 8 (April 2014): 1649–59. https://doi.org/10.1242/dev.100842.
Chakkalakal JV, Christensen J, Xiang W, Tierney MT, Boscolo FS, Sacco A, et al. Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state. Development. 2014 Apr;141(8):1649–59.
Chakkalakal, Joe V., et al. “Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state.Development, vol. 141, no. 8, Apr. 2014, pp. 1649–59. Pubmed, doi:10.1242/dev.100842.
Chakkalakal JV, Christensen J, Xiang W, Tierney MT, Boscolo FS, Sacco A, Brack AS. Early forming label-retaining muscle stem cells require p27kip1 for maintenance of the primitive state. Development. 2014 Apr;141(8):1649–1659.
Journal cover image

Published In

Development

DOI

EISSN

1477-9129

Publication Date

April 2014

Volume

141

Issue

8

Start / End Page

1649 / 1659

Location

England

Related Subject Headings

  • Stem Cells
  • Staining and Labeling
  • Phenotype
  • Muscular Dystrophy, Animal
  • Muscle, Skeletal
  • Mice, Inbred mdx
  • Mice, Inbred C57BL
  • Mice
  • Histones
  • Green Fluorescent Proteins