3 years ago

Redox-dependent BMI1 activity drives in vivo adult cardiac progenitor cell differentiation

Antonio Bernad, Francisco M. Cruz, Rosa María Carmona, Susana Cañón, María Tomé, Encarna Fuster, Enrique Roche, Diego Herrero
Accumulation of reactive oxygen species (ROS) is associated with several cardiovascular pathologies and with cell cycle exit by neonanatal cardiomyocytes, a key limiting factor in the regenerative capacity of the adult mammalian heart. The polycomb complex component BMI1 is linked to adult progenitors and is an important partner in DNA repair and redox regulation. We found that high BMI1 expression is associated with an adult Sca1+ cardiac progenitor sub-population with low ROS levels. In homeostasis, BMI1 repressed cell fate genes, including a cardiogenic differentiation program. Oxidative damage nonetheless modified BMI1 activity in vivo by derepressing canonical target genes in favor of their antioxidant and anticlastogenic functions. This redox-mediated mechanism is not restricted to damage situations, however, and we report ROS-associated differentiation of cardiac progenitors in steady state. These findings demonstrate how redox status influences the cardiac progenitor response, and identify redox-mediated BMI1 regulation with implications in maintenance of cellular identity in vivo.

Publisher URL: https://www.nature.com/articles/s41418-017-0022-2

DOI: 10.1038/s41418-017-0022-2

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