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

• DOI: 10.1242/dev.100842
• Publication Date: 2014-04-08T11:18:40Z
• Authors: Joe V. Chakkalakal; Josef Christensen; Wanyi Xiang; Mathew T. Tierney; Francesca S. Boscolo; Alessandra Sacco; Andrew S. Brack
• Keywords: Cyclin-Dependent Kinase Inhibitor p21; 0301 basic medicine; Staining and Labeling; Stem Cells; Green Fluorescent Proteins; Cell Differentiation; Muscular Dystrophy, Animal; Stem Cells and Regeneration; Histones; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Phenotype; Animals, Newborn; Disease Progression; Mice, Inbred mdx; Animals; Cell Lineage; Muscle, Skeletal; Cyclin-Dependent Kinase Inhibitor p27; Cell Proliferation

Across different niches, subsets of highly functional stem cells are maintained in a relatively dormant rather than proliferative state. Our understanding dynamics tissue-specific during conditions increased tissue turnover remains limited. Using TetO-H2B-GFP reporter history, we identify skeletal muscle cell, or satellite cells, that retain (LRC) lose (nonLRC) the H2B-GFP label. We show mice LRCs and nonLRCs formed at birth persist postnatal growth adult repair. Functionally, born equivalent transition maturation into distinct hierarchically organized subsets. Adult give rise to nonLRCs; former able self-renew, whereas latter restricted differentiation. Expression analysis revealed CIP/KIP family members p21cip1 (Cdkn1a) p27kip1 (Cdkn1b) be expressed higher levels LRCs. In accordance with crucial role LRC fate, loss promoted proliferation differentiation vitro impaired cell self-renewal after injury. By contrast, only affected nonLRCs, which myogenic commitment was inhibited. results provide evidence restriction potential is established early life through cycle inhibitor p27kip1. They also reveal differential discrete steps within hierarchy.