蒋卫 教授 武汉大学医学研究院
● 演讲题目:
《长非编码RNA与内胚层胰腺分化和糖尿病发生》
● 演讲摘要:
Long non-coding RNAs (lncRNAs) play crucial roles in regulating diverse biological processes including cell lineage specification and involve in disease pathogenesis.
Based on our previous work on human pancreatic differentiation, we have generated a comprehensive transcriptome profile of human pancreatic lineage including undifferentiated human embryonic stem cells (ESCs), ESC-derivate definitive endoderm, pancreatic progenitors, as well as purified human primary pancreatic alpha cells and beta cells. This data revealed dynamic regulation of hundreds of long non-coding RNAs (lncRNAs) during pancreatic lineage differentiation. More interestingly, dozens of endodermal pancreatic-specific lncRNAs exhibit genomic overlap with diabetes-associated SNPs revealed by GWAS database. One of them is the lncRNA DEANR1 (Definitive Endoderm Associated long Non-coding RNA1).
Our previous work has shown DEANR1 positively regulates the expression of its neighboring gene FOXA2, which is crucial for endoderm differentiation and pancreatic specification, and thus contributes to definitive endoderm differentiation. To further analyze the functional link between SNP/DEANR1 and pancreatic differentiation and diabetes pathogenesis, we have analyzed the regulatory effect of the SNP on DEANR1 expression. Moreover, we have generated the knock-in human ESC lines of the DEANR1-assocated SNP using CRISPR/cas9 genome editing technology with the aim that modeling disease in a dish based of in vitro pancreatic differentiation technology.
● 历年研究领域及成果介绍:
蒋卫博士在北京大学先后获得学士和博士学位,并在美国霍华德休斯医学研究中心、哈佛医学院完成博士后训练,2015起年任武汉大学医学研究院教授、武汉大学中南医院特聘研究员。十余年来蒋卫教授一直耕耘于细胞分化和表观遗传学研究,长期关注细胞命运决定这一基本的细胞生物学和发育生物学问题。
所取得的研究成果主要包括:系统建立多能干细胞(包括人/鼠/猴的ESC/iPSC)往胰腺方向分化的分步诱导方案,得到功能性的胰岛细胞,同时体外再现人内胚层、胰腺发育的过程;鉴定胰腺前体的表面标记CD24,使纯化胰腺前体细胞成为可能;发现可用于预测细胞分化潜能的简单生物标记分子WNT3,帮助选择具有合适谱系分化能力的人多能干细胞系;功能性鉴定人内胚层分化功能相关的组蛋白去甲基化酶KDM6和lncRNA分子DEANR1,探讨了内胚层命运决定的分子机制。
已发表20多篇论文,SCI引用数超过1400次。获邀在ISSCR会