| Literature DB >> 31591473 |
Kerstin Brinkmann1,2, Ashley P Ng1,2, Carolyn A de Graaf1,2, Ladina Di Rago1, Craig D Hyland1, Eugenio Morelli3,4, Jai Rautela1,2,5, Nicholas D Huntington1,2,5, Andreas Strasser1,2, Warren S Alexander1,2, Marco J Herold6,7.
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 expression of the miR17~92 cluster. Strikingly, loss of pro-apoptotic BIM completely prevented the loss of HSPCs caused by deletion of miR17~92. The BIM/miR17~92 interaction is conserved in human CD34+ HSPCs, as miR17~92 inhibition or blockade of its binding to the BIM 3'UTR reduced the survival and growth of these cells. Despite the prediction that miR17~92 functions by impacting a plethora of different targets, the absence of BIM alone is sufficient to prevent all defects caused by deletion of miR17~92 in haematopoietic cells.Entities:
Mesh：
Substances：
Year: 2019 PMID： 31591473 PMCID： PMC7206080 DOI： 10.1038/s41418-019-0430-6
Source DB: PubMed Journal: Cell Death Differ ISSN： 1350-9047 Impact factor: 15.828