长的非编码RNA在人定向型红系造血分化中的作用

项目名称： 长的非编码RNA在人定向型红系造血分化中的作用

项目编号： No.31471291

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 石莉红

作者单位： 中国医学科学院

项目金额： 85万元

中文摘要： 近年来，随着医疗技术的发展，人均寿命的延长和人口的老龄化，临床用血需求量急剧增加，全球范围都面临血荒危机。缓解血源短缺的一个有效途径是体外诱导多能造血干细胞定向分化为成熟红细胞。但是当前体外诱导分化体系还存在着诱导红细胞数目不足，分化红细胞生理功能不完全成熟等缺陷。这一体系的完善有赖于对红系分化转录调控网络的深刻认识。 长的非编码RNA（lncRNA）是转录调控网络的重要新成员，是决定谱系发育细胞命运的主要因素之一。截止目前，lncRNA在人红系分化过程的作用还没有得到系统深入的研究，具体调控人红系增殖和分化的lncRNA仍未见报道。我们的研究旨在填补这一空白。我们将利用RNA-seq建立人红系分化不同阶段lncRNA的表达图谱，同时结合权重基因网络分析的方法，筛选调控红细胞增殖和脱核的关键lncRNA,并进一步揭示它们的作用机制，从而为体外规模化诱导生理功能成熟的红细胞提供理论基础。

中文关键词： 长非编码RNA；细胞增殖与分化；定向型红系分化；人；转录调控

英文摘要： As a resource, blood has never been more in demand than it is today. While the worldwide blood demand keeps growing, population ageing leads to decrease the proportion of the young in population from whom most of our current blood donors come, significantly reducing the blood supply. A promising alternative strategy to supply substantial and safe red blood cells for clinical use is inducing the hematopoietic progenitor CD34+ cells differentiation into mature red blood cells ex vivo. Although CD34+ ex vivo differentiation system has been greatly improved previously, we still encounter the problems such as insufficent self-renewal of the erythroid progenitors and inefficient enucleation of the erythroid precursors. Resolving these problems will rely on a full appreciation of transcription regulatory network that determines erythroid lineage commitment and differentiation. Accumulating evidence indicates that lncRNAs play crucial roles in gene expression control during the differentiation processes. However, the roles of lncRNAs during human definitive erythroid differentiation are still largely unknown. In this study, we are going to identify the lncRNAs that regulate the self-renewal of the erythroid progenitors and the enucleation of the erythroid precursors during differentiation. We will then further reveal the underlying mechanisms of these candidate lncRNAs in order to shed more lights on the transcription regulatory network during erythropoiesis, which in turn would aid to more effetively improve the efficiency of ex vivo erythropoiesis for future clinical use.

英文关键词： lncRNA;cell proliferation and differentiation;definitive erythropoiesis;human;transcription regulation