lncRNA在干细胞多能性维持和质量差异中的作用与调控机制

诱导多能干细胞（iPS细胞）的出现意义重大，诱导技术日新月异，制约iPS细胞定向分化和临床研究及应用的一个关键因素是iPS细胞的质量。长链非编码RNA（lncRNA）作为基因表达调控和细胞命运决定的重要分子，信息量极其丰富且易于检测。我们初步分析发现干细胞最重要的干性因子Oct4/Sox2可直接激活linc1411和linc1422的表达，干扰这些lncRNA明显抑制干细胞多能性，还发现这些lncRNA可能与Sox2、miRNA和PRC2重要组分结合。在此基础上，本项目将通过ChIP、RIP和细胞功能实验等，确定lncRNA在干细胞多能性维持中的功能与调控机制，阐明lncRNA、转录因子、miRNAs和PRC2复合物间的作用模式，揭示它们在iPS细胞质量差异中的作用及机制。本项目的完成，不仅可以丰富干细胞多能性相关lncRNA机制的认识，还将为iPS细胞质量鉴定提供理论依据和可能的新方法。

Induced pluripotent stem cells (iPS cells) appear with significance, induced technologies are changing rapidly, a key factor in restricting directed differentiation, clinical research and application of iPS cells is the quality standards of iPS cells. Long non-coding RNA (lncRNA) as important molecules in regulating gene expression and cell fate decisions, has extremely rich amount of information and is easy to be detected. Our preliminary analysis found that Oct4/Sox2, the most important transcription factors for stem cells, can directly activate the expression of linc1411 and linc1422. Knockdown of these lncRNAs can significantly inhibit the pluripotency maintenance of stem cells. We also found that these lncRNAs could bind with Sox2, miRNAs and the important components of PRC2. On this basis, with ChIP, RIP and cell functional experiments, this project will determine the function and regulatory mechanism of lncRNA in stem cell pluripotency maintenance, clarify the functional model among lncRNA, transcription factors, miRNAs and the PRC2 complex, and investigate the role and mechanism of lncRNA in iPS cell quality difference. Completion of this project will not only enrich the understanding of lncRNA mechanism in regulating stem cell pluripotency, but also provide a theoretical basis and possible new approach for iPS cells qualification.