MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors
MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors
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DOI：
10.1016/j.devcel.2008.03.012
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发表时间：
2008-06-01
影响因子：
11.8
通讯作者：
Golub, Todd R.
中科院分区：
文献类型：
--
作者：
Lu, Jun;Guo, Shangqin;Golub, Todd R.
谱系特化是发育和再生生物学中的一个关键问题。我们假设microRNAs（miRNAs）是这些过程的重要参与者，并使用对造血中巨核细胞-红细胞祖细胞（MEP）的调控知之甚少作为模型系统。我们在这里报告，miR-150调节MEP的谱系命运。使用一种新的方法，能够在少数原代细胞中分析miRNA表达，我们确定miR-150优先在巨核细胞谱系中表达。通过功能获得和丧失实验，我们证明了miR-150在体外和体内以红系细胞为代价驱动MEP向巨核细胞分化。此外，我们确定了转录因子MYB作为miR-150在这种调节中的关键靶点。这些实验表明，miR-150调节MEP命运，从而确立了miRNA在哺乳动物多能细胞谱系特化中的作用。
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.