MicroRNA expression in maturing murine megakaryocytes

Abstract

MicroRNAs are small noncoding RNAs that regulate cellular development by interfering with mRNA stability and translation. We examined global microRNA expression during the differentiation of murine hematopoietic progenitors into megakaryocytes. Of 435 miRNAs analyzed, 13 were up-regulated and 81 were down-regulated. Many of these changes are consistent with miRNA profiling studies of human megakaryocytes and platelets, although new patterns also emerged. Among 7 conserved miRNAs that were up-regulated most strongly in murine megakaryocytes, 6 were also induced in the related erythroid lineage. MiR-146a was strongly up-regulated during mouse and human megakaryopoiesis but not erythropoiesis. However, overexpression of miR-146a in mouse bone marrow hematopoietic progenitor populations produced no detectable alterations in megakaryocyte development or platelet production in vivo or in colony assays. Our findings extend the repertoire of differentially regulated miRNAs during murine megakaryopoiesis and provide a useful new dataset for hematopoiesis research. In addition, we show that enforced hematopoietic expression of miR146a has minimal effects on megakaryopoiesis. These results are compatible with prior studies indicating that miR-146a inhibits megakaryocyte production indirectly by suppressing inflammatory cytokine production from innate immune cells, but cast doubt on a different study, which suggests that this miRNA inhibits megakaryopoiesis cell-autonomously. (Blood. 2010;116(23):e128-e138)

Systematic analysis of microRNA fingerprints in thrombocythemic platelets using integrated platforms

“…Of the 21-member list, only miR 490 displayed a generally restricted pattern of expression in Mk/platelets (relative to leukocytes), with no prior description of this miRNA in MPN studies, 5,6,34 and/or models of hematopoiesis 4,24 or megakaryocytic differentiation. 2,35,36 Given its aberrant expression during thrombocytosis, our data suggest that miR 490 represents a unique biomarker of exaggerated megakaryocytopoiesis and/or proplatelet formation, although its physiologic function(s) remain to be precisely elucidated. An in vitro differentiation model demonstrated progressive miR 490 down-regulations, results entirely consistent with the low-level expression seen in healthy controls during normal thrombopoiesis.…”

Thymosin β4 Up-regulation of MicroRNA-146a Promotes Oligodendrocyte Differentiation and Suppression of the Toll-like Proinflammatory Pathway

“…Lentiviral miR-146a transfection showed a 26-fold increase of wild-type miR-146a and attenuated the proliferation, migration, and tumorigenic potential of Ink4a/ Arf_/_ Pten_/_EgfrvIII murine astrocytes. Expression of miR146a in the hematopoietic system promotes macrophage development from hematopoietic stem cells, and down-regulation of miR-146a influences megakaryocytopoiesis (46). Forced expression of miR-146a in breast tumor cells inhibits endogenous NF-B expression and reduces metastatic activity of the tumor cells (47).…”

Expression and prognostic significance of microRNAs in Korean patients with myelodysplastic syndrome

“…74,78 In these later studies, it is possible that overexpression of miR-146a beyond endogenous levels is not sufficient to have a biological effect on megakaryocytes. An alternative interpretation claims that non-autonomous factors contribute to megakaryopoiesis and elevated platelets following knockdown of endogenous miR-146a.…”