The transcription factor NF-Y, composed by NF-YA, NF-YB and NF-YC subunits, has an important role in the regulation of cellular proliferation and differentiation in different cell types, among which muscle cells. While NF-YA, the DNA binding subunit of NF-Y, is down-regulated in the adult muscle of WT mice, its expression is observed in the mdx mouse, model for Duchenne Muscular Dystrophy, in which a massive regeneration mediated by resident muscle stem cells, namely Satellite Cells (SCs), occurs. With the aim to investigate the role of NF-YA in the SCs proliferation and differentiation, we generated and characterized a conditional knock out mouse model in which NF-YA is deleted in Pax7+ SCs by Tamoxifen induction in adult NF-YAflox/flox:Pax7CreER mice (NF-YA cKO). Cellular and molecular analysis carried out on isolated myofibers and SCs from WT and NF-YA cKO mice highlighted that NF-Y activity is important for the maintenance of SCs homeostasis. NF-YA loss depletes Pax7+ SCs pool and impairs SCs proliferation. Moreover, SCs-mediated regeneration following muscle damage induced by cardiotoxin is delayed in NF-YA cKO. The effect of NF-YA abrogation was also explored in post-natal muscle growth. Immunohistological analysis showed defects in muscle morphology and a decrease in SCs number in 3 weeks aged NF-YA cKO mice, period of major increment of muscle mass by SCs-mediated myonuclear accretion. The molecular mechanism underlying the impairment of SCs activity following NF-YA loss was investigated by AdenoCre-induced NF-YA deletion in ex vivo cultured SCs. Overall, our results highlight a role of NF-Y in muscle regeneration and in SCs fate, whose modulation could be useful to improve stem cell based therapies to treat muscular dystrophies.
The transcription factor NF-Y is required for satellite stem cell proliferation and skeletal muscle tissue repair / Rigillo, Giovanna; Basile, Valentina; Belluti, Silvia; Imbriano, Carol. - (2019). ((Intervento presentato al convegno ABCD 2019 CONGRESS tenutosi a Bologna nel 19-21 settembre 2019.
|Data di pubblicazione:||2019|
|Titolo:||The transcription factor NF-Y is required for satellite stem cell proliferation and skeletal muscle tissue repair|
|Autore/i:||Rigillo, Giovanna; Basile, Valentina; Belluti, Silvia; Imbriano, Carol|
|Nome del convegno:||ABCD 2019 CONGRESS|
|Data del convegno:||19-21 settembre 2019|
|Luogo del convegno:||Bologna|
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