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Publication : The transcription factor NF-Y participates to stem cell fate decision and regeneration in adult skeletal muscle.

First Author  Rigillo G Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  6013
PubMed ID  34650038 Mgi Jnum  J:312426
Mgi Id  MGI:6787550 Doi  10.1038/s41467-021-26293-w
Citation  Rigillo G, et al. (2021) The transcription factor NF-Y participates to stem cell fate decision and regeneration in adult skeletal muscle. Nat Commun 12(1):6013
abstractText  The transcription factor NF-Y promotes cell proliferation and its activity often declines during differentiation through the regulation of NF-YA, the DNA binding subunit of the complex. In stem cell compartments, the shorter NF-YA splice variant is abundantly expressed and sustains their expansion. Here, we report that satellite cells, the stem cell population of adult skeletal muscle necessary for its growth and regeneration, express uniquely the longer NF-YA isoform, majorly associated with cell differentiation. Through the generation of a conditional knock out mouse model that selectively deletes the NF-YA gene in satellite cells, we demonstrate that NF-YA expression is fundamental to preserve the pool of muscle stem cells and ensures robust regenerative response to muscle injury. In vivo and ex vivo, satellite cells that survive to NF-YA loss exit the quiescence and are rapidly committed to early differentiation, despite delayed in the progression towards later states. In vitro results demonstrate that NF-YA-depleted muscle stem cells accumulate DNA damage and cannot properly differentiate. These data highlight a new scenario in stem cell biology for NF-Y activity, which is required for efficient myogenic differentiation.
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