miR17~92 is essential for the survival of hematopoietic stem and progenitor cells by restraining pro-apoptotic BIM
Kerstin Brinkmann, Craig Hyland, Carolyn A de Graaf, Andreas Strasser, Warren S Alexander and Marco J Herold
Received: 29th May 18
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 (miR17~92Δfl/Δfl) had no impact on their lifespan or general well-being. However, detailed analysis of the hematopoietic system in miR17~92Δfl/Δfl 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.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.