Cruz, Francisco MiguelTome, MariaBernal, Juan AntonioBernad, Antonio2017-11-272017-11-272015Cell Death Dis. 2015; 6:e19532041-4889http://hdl.handle.net/20.500.12105/5384B lymphoma Mo-MLV insertion region 1 (Bmi1) is a polycomb-family transcriptional factor critical for self-renewal in many adult stem cells and human neoplasia. We sought to identify microRNAs regulated by Bmi1 that could play a role in multipotent cardiac progenitor cell (CPC) decisions. We found that miR-300, a poorly characterized microRNA mapping in the Dlk1-Dio3 microRNA cluster, was positively regulated by Bmi1 in CPCs. Forced expression of miR-300 in CPCs promoted an improved stemness signature with a significant increase in Oct4 levels, a reduction in senescence progression and an enhanced proliferative status via p19 activation and inhibition of p16 accumulation. Endothelial and cardiogenic differentiation were clearly compromised by sustained miR-300 expression. Additionally, RNA and protein analysis revealed a significant reduction in key cardiac transcription factors, including Nkx2.5 and Tbx5. Collectively, these results suggest that some functions attributed to Bmi1 are due to induction of miR-300, which decreases the cardiogenic differentiation potential of multipotent CPCs in vitro and promotes self-renewal.engVoRhttp://creativecommons.org/licenses/by/4.0/CELL SELF-RENEWALRANDOMIZED PHASE-1 TRIALACTIVATED PROTEIN-KINASEINTESTINAL STEM-CELLSMYOCARDIAL-INFARCTIONHEARTPATHWAYCANCERCARDIOMYOPATHYCARDIOMYOCYTESAtribución 4.0 Internacional26512961610.1038/cddis.2015.255Cell Death & Differentiationopen access