PUBLICATION
Macrophage development from hematopoietic stem cells requires PU.1 coordinated microRNA expression
- Authors
- Ghani, S., Riemke, P., Schönheit, J., Lenze, D., Stumm, J., Hoogenkamp, M., Lagendijk, A., Heinz, S., Bonifer, C., Bakkers, J., Abdelilah-Seyfried, S., Hummel, M., and Rosenbauer, F.
- ID
- ZDB-PUB-110713-30
- Date
- 2011
- Source
- Blood 118(8): 2275-84 (Journal)
- Registered Authors
- Abdelilah-Seyfried, Salim, Bakkers, Jeroen
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics
- Cell Line
- Cell Lineage/genetics
- Hematopoietic Stem Cells/cytology*
- Hematopoietic Stem Cells/metabolism*
- In Vitro Techniques
- Macrophages, Peritoneal/cytology*
- Macrophages, Peritoneal/metabolism*
- Mice
- Mice, Inbred C57BL
- MicroRNAs/genetics*
- Myelopoiesis/genetics
- Proto-Oncogene Proteins/antagonists & inhibitors
- Proto-Oncogene Proteins/genetics*
- RNA, Small Interfering/genetics
- Trans-Activators/antagonists & inhibitors
- Trans-Activators/genetics*
- Zebrafish/embryology
- Zebrafish/genetics
- PubMed
- 21730352 Full text @ Blood
Citation
Ghani, S., Riemke, P., Schönheit, J., Lenze, D., Stumm, J., Hoogenkamp, M., Lagendijk, A., Heinz, S., Bonifer, C., Bakkers, J., Abdelilah-Seyfried, S., Hummel, M., and Rosenbauer, F. (2011) Macrophage development from hematopoietic stem cells requires PU.1 coordinated microRNA expression. Blood. 118(8):2275-84.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping