MicroRNA-146a disrupts hematopoietic differentiation and survival

Objective MicroRNAs (miRNAs) are short noncoding RNAs capable of exerting dramatic effects by postranscriptionally regulating numerous messenger RNA targets. Toll-like receptor-4 (TLR-4) activation by lipopolysaccharide (LPS) induces the expression of three miRNAs in myeloid cells. The aim of this s...

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Bibliographic Details
Published in:Experimental hematology 2011-02, Vol.39 (2), p.167-178.e4
Main Authors: Starczynowski, Daniel T, Kuchenbauer, Florian, Wegrzyn, Joanna, Rouhi, Arefeh, Petriv, Oleh, Hansen, Carl L, Humphries, R. Keith, Karsan, Aly
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Base Sequence
Bone Marrow - metabolism
Cell Differentiation
Cell Survival
Erythroid Cells - cytology
Erythroid Cells - metabolism
Gene Expression Profiling
Hematology, Oncology and Palliative Medicine
Hematopoiesis - genetics
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Lymphocytes - cytology
Lymphocytes - metabolism
Mice
Mice, Inbred C57BL
MicroRNAs - genetics
MicroRNAs - metabolism
Molecular Sequence Data
Up-Regulation
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Summary:Objective MicroRNAs (miRNAs) are short noncoding RNAs capable of exerting dramatic effects by postranscriptionally regulating numerous messenger RNA targets. Toll-like receptor-4 (TLR-4) activation by lipopolysaccharide (LPS) induces the expression of three miRNAs in myeloid cells. The aim of this study was to investigate the in vivo consequences of expressing one of the LPS-induced miRNA, miR-146a, in bone marrow cells. Material and Methods The role of miR-146a in hematopoiesis was investigated by using retroviral infection and overexpression of miR-146a in mouse hematopoietic stem/progenitor cells, followed by bone marrow transplantations. Results miR-146a is mainly expressed in primitive hematopoietic stem cells and T lymphocytes. Overexpression of miR-146a in hematopoietic stem cells, followed by bone marrow transplantation, resulted in a transient myeloid expansion, decreased erythropoiesis, and impaired lymphopoiesis in select anatomical locations. Enforced expression of miR-146a also impaired bone marrow reconstitution in recipient mice and reduced survival of hematopoietic stem cells. Conclusions Our results indicate that miR-146a, an LPS-induced miRNA, regulates multiple aspects of hematopoietic differentiation and survival. Furthermore, the consequences of miR-146a expression in hematopoietic cells mimics some of the reported effects with acute LPS exposure.
ISSN:0301-472X
1873-2399
DOI:10.1016/j.exphem.2010.09.011