MicroRNAs control the apoptotic threshold in primed Pluripotent stem cells through regulation of BIM

被引:42
作者
Pernaute, Barbara [1 ]
Spruce, Thomas [1 ]
Smith, Kimberley M. [2 ]
Sanchez-Nieto, Juan Miguel [1 ]
Manzanares, Miguel [3 ]
Cobb, Bradley [2 ]
Rodriguez, Tristan A. [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, British Heart Fdn, Ctr Res Excellence, Imperial Ctr Translat & Expt Med,Natl Heart & Lun, London W12 0NN, England
[2] Univ London Royal Vet Coll, London NW1 0TU, England
[3] CNIC, Dept Cardiovasc Dev & Repair, Madrid 28029, Spain
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
epiblast; pluripotency; apoptosis; microRNAs; Bim; Dicer; MOUSE DEVELOPMENT; DNA METHYLATION; MIRNA CLUSTERS; DICER; FAMILY; DIFFERENTIATION; AUTOIMMUNITY; EXPRESSION; DISEASE; LINEAGE;
D O I
10.1101/gad.245621.114
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mammalian primed pluripotent stem cells have been shown to be highly susceptible to cell death stimuli due to their low apoptotic threshold, but how this threshold is regulated remains largely unknown. Here we identify microRNA (miRNA)-mediated regulation as a key mechanism controlling apoptosis in the post-implantation epiblast. Moreover, we found that three miRNA families, miR-20, miR-92, and miR-302, control the mitochondrial apoptotic machinery by fine-tuning the levels of expression of the proapoptotic protein BIM. These families therefore represent an essential buffer needed to maintain cell survival in stem cells that are primed for not only differentiation but also cell death.
引用
收藏
页码:1873 / 1878
页数:6
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