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bioRxiv · 10.1101/342071

miR17~92 is essential for the survival of hematopoietic stem and progenitor cells by restraining pro-apoptotic BIM

Brinkmann, K.·Hyland, C.·de Graaf, C. A.·Strasser, A.·Alexander, W. S.·Herold, M. J.
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Abstract

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 [Formula] had no impact on their lifespan or general well-being. However, detailed analysis of the hematopoietic system in [Formula] 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.

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Brinkmann, K., Hyland, C., de Graaf, C. A., Strasser, A., Alexander, W. S., Herold, M. J.. 2018-06-08. miR17~92 is essential for the survival of hematopoietic stem and progenitor cells by restraining pro-apoptotic BIM. https://doi.org/10.1101/342071

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