RT Journal Article SR Electronic T1 miR17~92 is essential for the survival of hematopoietic stem and progenitor cells by restraining pro-apoptotic BIM JF bioRxiv FD Cold Spring Harbor Laboratory SP 342071 DO 10.1101/342071 A1 Kerstin Brinkmann A1 Craig Hyland A1 Carolyn A de Graaf A1 Andreas Strasser A1 Warren S Alexander A1 Marco J Herold YR 2018 UL http://biorxiv.org/content/early/2018/06/08/342071.abstract AB The micro RNA cluster miR17~92, also known as oncomiR-1, impacts diverse cellular processes, such as cell survival and proliferation. Constitutive loss of miR17~92 in mice causes severe defects in skeletal development, organ development and hematopoiesis, resulting in early post-natal lethality. The critical functions of miR17~92 in a fully developed animal have not yet been explored. Here we show that deletion of miR17~92 in adult mice had no impact on their lifespan or general well-being. However, detailed analysis of the hematopoietic system in mice, revealed a dramatic reduction in all mature hematopoietic lineages, which was due to the loss of early hematopoietic stem/progenitor cells (HSPCs). Strikingly, the concomitant loss of the pro-apoptotic BH3-only protein BIM rescued the loss of the HSPCs and all of their differentiated progeny that was caused by the deletion of miR17~92. These findings demonstrate that miR17~92 is critical for the survival of HSPCs by restraining the activity of the pro-apoptotic BH3-only protein BIM.