Haematopoietic Stem Cell Laboratory, MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Blood. 2012 Sep 20;120(12):2412-6. doi: 10.1182/blood-2011-10-383653. Epub 2012 Aug 6.
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.
MicroRNAs (miRs) 参与正常和恶性造血的多个方面，包括造血干细胞 (HSC) 的自我更新、增殖和终末分化。然而，miR 在 HSC 产生最早的谱系定向祖细胞中的作用尚未确定。使用 Dicer 失活，我们表明 miR 复合物不仅对 HSC 的维持至关重要，而且对其红细胞编程和随后的定向红细胞祖细胞生成是特异性所必需的。在双潜能前 MegE 中，Dicer 的缺失上调了优先在巨核细胞祖细胞中表达的转录因子（Gata2 和 Zfpm1），并降低了红细胞特异性 Klf1 转录因子的表达。这些结果表明 Dicer 在获得红细胞谱系编程和 HSC 及其随后的红细胞谱系分化中的特定要求，并且特别表明 miR 复合物在实现维持 HSC 多谱系潜能所需的谱系特异性转录调节剂的适当平衡方面发挥作用。
