Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Curr Opin Hematol. 2012 Jul;19(4):261-7. doi: 10.1097/MOH.0b013e328353d4e9.
Recent data show that microRNAs play critical roles in the regulation of the developmental process of hematopoietic stem and progenitor cells toward mature myeloid cells. The main focus of the article is the function of some evolutionary conserved microRNAs that are abundantly expressed and tightly regulated during myelopoiesis.
Global microRNA depletion studies in hematopoietic stem cells have shown the importance of microRNA-controlled pathways for hematopoiesis. Recent insights from genetic mouse models and overexpression or deletion of microRNAs in developmental cell intermediates demonstrate strong evidence for evolutionary conserved microRNA-regulated pathways involved in tight control of cellular processes such as proliferation, differentiation and apoptosis at different stages of blood cell development. It is becoming evident that the myeloid transcription factor PU.1 regulates the expression of critical microRNAs including miR-17∼92 and miR-146a during myelopoiesis. Furthermore, there is evidence for the contribution of aberrant miR-125 activities in hematopoietic disorders including myeloid leukemia.
Despite the large number of articles describing differential microRNA expression during hematopoiesis, microRNA functions and their downstream pathways in myeloid lineage decisions and leukemia are only recently emerging. Here we discuss new findings concerning PU.1-controlled microRNAs and miR-125-regulated networks in normal and malignant myelopoiesis.
最近的数据表明, microRNAs 在造血干细胞向成熟髓系细胞的发育过程中发挥着关键作用。本文的主要焦点是一些进化上保守的 microRNAs 的功能,这些 microRNAs 在髓系细胞生成过程中大量表达且受到严格调控。
在造血干细胞中进行的全局 microRNA 耗竭研究表明, microRNA 控制的途径对造血具有重要意义。来自遗传小鼠模型的最新研究结果以及在发育细胞中间产物中过表达或缺失 microRNAs ,都有力地证明了进化上保守的 microRNA 调控途径在严格控制细胞过程中发挥着重要作用,如增殖、分化和细胞凋亡等,这些过程在血细胞发育的不同阶段都会发生。目前已经很明显,髓系转录因子 PU.1 调节关键 microRNAs 的表达,包括 miR-17∼92 和 miR-146a 在髓系细胞生成过程中。此外,在包括髓性白血病在内的造血紊乱中,也有证据表明异常的 miR-125 活性发挥了作用。
尽管有大量的文章描述了造血过程中 microRNA 的差异表达,但 microRNA 的功能及其在髓系谱系决策和白血病中的下游途径直到最近才开始出现。在这里,我们讨论了与正常和恶性髓系细胞生成中 PU.1 控制的 microRNAs 和 miR-125 调控网络有关的新发现。