microRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors

Developmental Cell (2008), doi:10.1016/j.devcel.2008.03.012. Published: 2008.06.09

Jun Lu, Shangqin Guo, Benjamin L. Ebert, Hao Zhang, Xiao Peng, Jocelyn Bosco, Jennifer Pretz, Rita Schlanger, Judy Y. Wang, Raymond H. Mak, David M. Dombkowski, Frederic I. Preffer, David T. Scadden and Todd R. Golub

Abstract

Lineage specification is a critical issue in developmental and regenerative biology. We hypothesized that microRNAs (miRNAs) are important participants in that process and used the poorly-understood regulation of megakaryocyte-erythrocyte progenitors (MEPs) in hematopoiesis as a model system. We report here that miR-150 modulates lineage fate in MEPs. Using a novel methodology capable of profiling miRNA expression in limiting numbers of primary cells, we identify miR-150 as preferentially expressed in the megakaryocytic lineage. Through gain- and loss-of-function experiments, we demonstrate that miR-150 drives MEP differentiation toward megakaryocytes at the expense of erythroid cells in vitro and in vivo. Moreover, we identify the transcription factor MYB as a critical target of miR-150 in this regulation. These experiments show that miR-150 regulates MEP fate, and thus establish a role for miRNAs in lineage specification of mammalian multi-potent cells.

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Supplemental Data

Description Link/Filename
Supplemental Data in pdf Lu_Supplemental_Data_dev_cell.pdf
Table S1 Supplementary_Table1.xls
Table S2 Supplementary_Table2.xls
Table S3 Supplementary_Table3.xls
Table S4, normalized expression data megamiR_data.normalized.log2.th6.gct