miR17~92 restrains pro-apoptotic BIM to ensure survival of haematopoietic stem and progenitor cells

K Brinkmann; AP Ng; CA de Graaf; L Di Rago; CD Hyland; E Morelli; J Rautela; ND Huntington; A Strasser; WS Alexander; MJ Herold

Journal article

miR17~92 restrains pro-apoptotic BIM to ensure survival of haematopoietic stem and progenitor cells

K Brinkmann, AP Ng, CA de Graaf, L Di Rago, CD Hyland, E Morelli, J Rautela, ND Huntington, A Strasser, WS Alexander, MJ Herold

Cell Death and Differentiation | NATURE PUBLISHING GROUP | Published : 2020

DOI: 10.1038/s41418-019-0430-6

Abstract

The miR17~92 cluster plays important roles in haematopoiesis. However, it is not clear at what stage of differentiation and through which targets miR17~92 exerts this function. Therefore, we generated miR17~92fl/fl; RosaCreERT2 mice for inducible deletion of miR17~92 in haematopoietic cells. Bone marrow reconstitution experiments revealed that miR17~92-deleted cells were not capable to contribute to mature haematopoietic lineages, which was due to defects in haematopoietic stem/progenitor cells (HSPCs). To identify the critical factor targeted by miR17~92 we performed gene expression analysis in HSPCs, demonstrating that mRNA levels of pro-apoptotic Bim inversely correlated with the expressi..

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