Dicer is selectively important for the earliest stages of erythroid development
Dicer is selectively important for the earliest stages of erythroid development
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DOI：
10.1182/blood-2011-10-383653
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发表时间：
2012-09-20
期刊：
影响因子：
20.3
通讯作者：
Nerlov, Claus
中科院分区：
文献类型：
--
作者：
Buza-Vidas, Natalija;Cismasiu, Valeriu B.;Nerlov, Claus
MicroRNAs(MiRs)参与正常和恶性造血的许多方面，包括造血干细胞(HSC)的自我更新、增殖和终末分化。然而，MIR在从造血干细胞产生早期血统承诺的祖细胞的过程中的作用尚未确定。利用DICER失活，我们证明miR复合体不仅对于HSC的维持是必不可少的，而且对于他们的红系编程和随后承诺的红系祖细胞的产生是特别需要的。在双能前MEGES中，Dice的缺失上调了转录因子在巨核祖细胞(Gata2和Zfpm1)中的优先表达，并降低了红系特异性KLF1转录因子的表达。这些结果表明，在获得红系编程和HSC及其随后的红系分化的潜力方面，DICER具有特定的要求，特别是表明miR复合体在实现维持HSC多系潜能所需的谱系特异性转录调节因子的适当平衡中发挥了作用。(血。2012；120(12)：2412-2416)
MicroRNAs (miRs) are involved in many aspects of normal and malignant hematopoiesis, including hematopoietic stem cell (HSC) self-renewal, proliferation, and terminal differentiation. However, a role for miRs in the generation of the earliest stages of lineage committed progenitors from HSCs has not been identified. Using Dicer inactivation, we show that the miR complex is not only essential for HSC maintenance but is specifically required for their erythroid programming and subsequent generation of committed erythroid progenitors. In bipotent pre-MegEs, loss of Dicer up-regulated transcription factors preferentially expressed in megakaryocyte progenitors (Gata2 and Zfpm1) and decreased expression of the erythroid-specific Klf1 transcription factor. These results show a specific requirement for Dicer in acquisition of erythroid lineage programming and potential in HSCs and their subsequent erythroid lineage differentiation, and in particular indicate a role for the miR complex in achieving proper balance of lineage-specific transcriptional regulators necessary for HSC multilineage potential to be maintained. (Blood. 2012;120(12):2412-2416)