title: 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 miR-146a 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.
authors: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors: Joanna B
authors: JB
authors: Opalinska
authors: Alexey
authors: A
authors: Bersenev
authors: Zhe
authors: Z
authors: Zhang
authors: Alec A
authors: AA
authors: Schmaier
authors: John
authors: J
authors: Choi
authors: Yu
authors: Y
authors: Yao
authors: Janine
authors: J
authors: D'Souza
authors: Wei
authors: W
authors: Tong
authors: Mitchell J
authors: MJ
authors: Weiss
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002469:Cell Separation; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D034061:Thrombopoiesis / Q000235:genetics*
chemical_list: D035683:MicroRNAs