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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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