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

Giovanna Rigillo, Valentina Basile, Silvia Belluti, Mirko Ronzio, Elisabetta Sauta, Alessia Ciarrocchi, Lucia Latella, Marielle Saclier, Susanna Molinari, Antonio Vallarola, Graziella Messina, Roberto Mantovani, Diletta Dolfini and Carol Imbriano ()
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Giovanna Rigillo: University of Modena and Reggio Emilia
Valentina Basile: University of Modena and Reggio Emilia
Silvia Belluti: University of Modena and Reggio Emilia
Mirko Ronzio: University of Milan
Elisabetta Sauta: University of Pavia
Alessia Ciarrocchi: Laboratory of Translational Research, Azienda USL-IRCCS
Lucia Latella: Institute of Translational Pharmacology, Italian National Research Council and Epigenetics and Regenerative Medicine, IRCCS Fondazione Santa Lucia
Marielle Saclier: University of Milan
Susanna Molinari: University of Modena and Reggio Emilia
Antonio Vallarola: University of Modena and Reggio Emilia
Graziella Messina: University of Milan
Roberto Mantovani: University of Milan
Diletta Dolfini: University of Milan
Carol Imbriano: University of Modena and Reggio Emilia

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-26293-w

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