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

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

来源：Developmental Cell, 2008, 14(6): 843-853.

DOI：10.1016/j.devcel.2008.03.012

Lineage specification is a critical issue in developmental and regenerative biology. We hypothesized that microRNAs (miRNAs) are important participants in those processes 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 small 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 multipotent cells.

• 出版日期2008-6
• 单位MIT