miR-125b调控红细胞脱核成熟的作用及其机制研究

项目名称： miR-125b调控红细胞脱核成熟的作用及其机制研究

项目编号： No.31301199

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 谢小燕

作者单位： 中国人民解放军军事医学科学院

项目金额： 28万元

中文摘要： 诱导干细胞红系分化可能解决目前临床血供短缺的问题，但是如何提高红细胞成熟和脱核效率是该技术中一个急待解决的关键问题。我们试图利用miR-125b 来提高红细胞成熟的效率。已有研究显示miR-125b能通过靶向凋亡相关基因调节造血干细胞的增殖和动态平衡。我们前期的研究发现，miR-125b 具有促红细胞成熟和脱核的潜能，在成熟红细胞中有miR-125b 的富集，而在成红细胞或红白血病细胞系中过表达miR-125b 也能促进细胞的成熟和脱核，抑制其表达则出现相反效果，Bcl-2和SMARCD2可能参与了这个过程。本课题将通过转基因实现miR-125b 功能的缺失或获得（LOF/GOF）确定其对红细胞脱核的作用，进一步利用信息学和靶基因LOF/GOF 确定在红细胞脱核成熟过程中发挥关键作用的miR-125b 靶基因，研究脱核的细胞及分子机制，最终提高体外诱导红细胞成熟的效率，满足临床应用需求。

中文关键词： miR-125b；红细胞；脱核；成熟；Bcl-2

英文摘要： To overcome the shortage of blood transfusions in the treatment of anemia and regular surgery, it is necessary to explore new source of red blood cells (RBCs). Although ex vivo derivation of RBCs from stem cells (embryonic stem cells or hematopoietic stem cells) is under investigation, there are still plenty of hurdles needed to be strided over before these RBCs show their clinical usages. Among these hurdles, enucleation remains one of the critical rate-limiting steps of in vitro RBC synthesis. We propose to take advantage of microRNA to improve the maturation and enucleation of erythrocytes, especially miR-125b. microRNAs are small RNA molecules binding to partially complementary sites in the 3'-UTR of target transcripts and repressing their expression, they have been shown as important regulators in stem cell commitment, cell proliferation and apoptosis. Provious studies from other groups and our lab showed that miR-125b is a pivotal regulator in hematopoietic stem cell homeostasis as well as proapoptosis/ anti-apoptosis gene and cell cycle regulator in different cancer cells depending on the intracellular environment. More importantly, we discovered the relationship between miR-125b and enucleation. Mature miR-125b was enriched in RBCs, and the overexpression of miR-125b improved the erythroid maturation and

英文关键词： miR-125b；erythrocytes；enucleation；maturation；Bcl-2