Journal article

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

Kerstin Brinkmann, Ashley P Ng, Carolyn A de Graaf, Ladina Di Rago, Craig D Hyland, Eugenio Morelli, Jai Rautela, Nicholas D Huntington, Andreas Strasser, Warren S Alexander, Marco J Herold

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

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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