miR17~92 restrains pro-apoptotic BIM to ensure survival of haematopoietic stem and progenitor cells
Journal Title
Cell Death and Differentiation
Publication Type
Journal Article
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 miR17~92(fl/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.
Publisher
Springer Nature
WEHI Research Division(s)
Blood Cells And Blood Cancer; Immunology
PubMed ID
31591473
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2019-10-23 02:22:49
Last Modified: 2019-10-23 02:30:23
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