Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 35, Issue 17, Pages 2892-2909Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00536-15
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Funding
- Ministerio de Economia y Competitividad, Gobierno de Espana [BFU2012-38111]
- Junta de Andalucia [CTS-1614, CTS-8053, BIO-302]
- AFM [AFM2012-16074]
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The acquisition of a proliferating-cell status from a quiescent state as well as the shift between proliferation and differentiation are key developmental steps in skeletal-muscle stem cells (satellite cells) to provide proper muscle regeneration. However, how satellite cell proliferation is regulated is not fully understood. Here, we report that the c-isoform of the transcription factor Pitx2 increases cell proliferation in myoblasts by downregulating microRNA 15b (miR-15b), miR-23b, miR-106b, and miR-503. This Pitx2c-microRNA (miRNA) pathway also regulates cell proliferation in early-activated satellite cells, enhancing Myf5(+) satellite cells and thereby promoting their commitment to a myogenic cell fate. This study reveals unknown functions of several miRNAs in myoblast and satellite cell behavior and thus may have future applications in regenerative medicine.
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