Macrophage development from hematopoietic stem cells requires PU.1 coordinated microRNA expression

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Item Type:	Article
Title:	Macrophage development from hematopoietic stem cells requires PU.1 coordinated microRNA expression
Creators Name:	Ghani, S., Riemke, P., Schoenheit, J., Lenze, D., Stumm, J., Hoogenkamp, M., Lagendijk, A., Heinz, S., Bonifer, C., Bakkers, J., Abdelilah-Seyfried, S., Hummel, M. and Rosenbauer, F.
Abstract:	The differentiation of hematopoietic stem cells (HSC) into myeloid lineages requires the transcription factor PU.1. While PU.1-dependent induction of myeloid-specific target genes has been intensively studied, negative regulation of stem cell or alternate lineage programs remains incompletely characterized. To test for such negative regulatory events, we searched for PU.1-controlled microRNAs (miRs) by expression profiling using a PU.1-inducible myeloid progenitor cell line model. We provide evidence that PU.1 directly controls expression of at least four of these miRs (miR-146a, miR-342, miR-338 and miR-155) through temporally dynamic occupation of binding sites within regulatory chromatin regions adjacent to their genomic coding loci. Ectopic expression of the most robustly induced PU.1 target miR, miR-146a, directed the selective differentiation of HSC into functional peritoneal macrophages in mouse transplantation assays. In line with this observation, disruption of Dicer expression or specific antagonization of miR-146a function inhibited the formation of macrophages during early zebrafish development. Collectively, we delineate a PU.1-orchestrated miR program which mediates key functions of PU.1 during myeloid differentiation.
Keywords:	PU.1, microRNA, Hematopoiesis, Myeloid Differentiation, Animals, Mice, Zebrafish
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	118
Number:	8
Page Range:	2275-2284
Date:	25 August 2011
Official Publication:	https://doi.org/10.1182/blood-2011-02-335141
PubMed:	View item in PubMed

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