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水生所11月16日创新系列讲座预告(2016-10)
作者: | 2016-11-14 | 浏览量:

  时间:2016年11月16日 星期三 上午10:00

  地点:1号实验楼 8楼学术报告厅

  报告专家:汤富酬 研究员 北京大学生命科学学院BIOPIC中心

  报告题目:利用单细胞功能基因组学技术研究人类早期胚胎发育

  专家简介:

  汤富酬研究员2010年在英国剑桥大学Gurdon研究所完成博士后工作,随后供职于北京大学生物动态光学成像中心(BIOPIC)并担任研究员,2015年起在北大-清华生命科学联合中心任研究员,2016年8月至今在北大未来基因诊断高精尖创新中心任研究员。汤富酬研究员的项目成果“精确推演母源基因组信息”于2015年入选“2014年度中国科学十大进展”,次年,项目成果“揭示人类原始生殖细胞基因表达与表观遗传调控特征”入选“2015年度中国科学十大进展”。2016年汤富酬研究员获国家自然科学基金委杰出青年基金项目资助;11月10日获“谈家桢生命科学创新奖”。

  具有自我更新能力和分化潜能的干细胞是哺乳动物胚胎发育过程中以及成体中的关键种类的细胞,对各种干细胞进行深入研究是理解哺乳动物发育、生长机制的关键,也是将干细胞应用于临床再生医学、治疗人类疾病的前提。汤富酬研究员的科研团队主要围绕哺乳动物早期胚胎发育研究多能性干细胞分化、发育调控的分子机理,特别是表观遗传学调控机理,以及相关的原始生殖细胞(Primordial Germ cells)发育过程中的表观遗传学重编程机理。利用团队发展的单细胞转录组测序技术(single cell RNA-Seq transcriptome analysis)、单细胞DNA甲基化组分析技术(Single cell RRBS),以及单细胞基因组测序技术(Single cell genome sequencing)、染色体免疫共沉淀-测序技术(ChIP-Seq)、早期胚胎显微操作技术深入分析哺乳动物早期胚胎以及多能性干细胞中基因表达网络的表观遗传学调控机理。

  报告摘要:

  Measuring gene expression in individual cells is crucial for understanding the gene regulatory network controlling human embryonic development. We applied single-cell RNA -Seq analysis to human preimplantation embryos, primordial germ cells (PGCs), and human embryonic stem cells (hESCs). We also systematically profiled the DNA methylome of human early embryos from the zygotic stage through to post-implantation. We showed that the major wave of genome-wide demethylation is complete at the 2-cell stage, contrary to previous observations in mice. Moreover, the demethylation of the paternal genome was much faster than that of the maternal genome, and by the end of the zygotic stage the genome-wide methylation level in male pronuclei was already lower than that in female pronuclei. Then we also showed that long interspersed nuclear elements (LINEs) or short interspersed nuclear elements (SINEs) that were evolutionarily young are demethylated to a milder extent compared to older elements in the same family and had higher abundance of transcripts, indicating that early embryos tend to retain higher residual methylation at the evolutionarily younger and more active transposable elements. Furthermore, we analyzed the DNA methylome of human PGCs and found global demethylation of their genomes. Approximately 10 to 11 weeks after gestation, the PGCs were nearly devoid of any DNA methylation, whereas the repeat elements still kept high level of residual methylation. Our work provides insights of critical features of the transcriptome and DNA methylome landscapes of human early embryos and primordial germ cells, as well as the functional significance of DNA methylome to regulation of gene expression and repression of transposable elements.

  代表性发表文章:

  Zhou F, Li X, Wang W, Zhu P, Zhou J, He W, Ding M, Xiong F, Zheng X, Li Z, Ni Y, Mu X, Wen L, Cheng T, Lan Y, Yuan W*, Fuchou Tang*, Liu B*. Tracing haematopoietic stem cell formation at single-cell resolution. Nature, 533: 487-492 (2016) (*: 共同通讯作者).

  Fan X, Zhang X, Wu X, Guo H, Hu Y, Tang Fuchou*, Huang Y*. Single-cell RNA-seq transcriptome analysis of linear and circular RNAs in mouse preimplantation embryos. Genome Biology 16: 148 (2015) (*: 共同通讯作者).

  Guo H, Zhu P, Guo F, Li X, Wu X, Fan X, Wen L*, Tang Fuchou*. Profiling DNA methylome landscapes of mammalian cells with single-cell reduced-representation bisulfite sequencing. Nature Protocols 10: 645-659 (2015) (*: 共同通讯作者).

  Wen L*, Tang Fuchou*, How to catch rare cell types. Nature 2015; doi:10.1038/nature15204 (*: Co-corresponding authors) (Preview).

  Guo F, Yan L, Guo H, Li L, Hu B, Zhao Y, Yong J, Hu Y, Wang X, Wei Y, Wang W, Li R, Yan J, Zhi X, Zhang Y, Jin H, Zhang W, Hou Y, Zhu P, Li J, Zhang L, Liu S, Ren Y, Zhu X, Wen L, Gao YQ, Tang Fuchou*, Qiao J*. The transcriptome and DNA methylome landscapes of human primordial germ cells. Cell 2015; 161: 1437-1452 (*: Co-corresponding authors).

  Zhang W, Li J, Suzuki K, Qu J, Wang P, Zhou J, Liu X, Ren R, Xu X, Ocampo A, Yuan T, Yang J, Li Y, Shi L, Guan D, Pan H, Duan S, Ding Z, Li M, Yi F, Bai R, Wang Y, Chen C, Yang F, Li X, Wang Z, Aizawa E, Goebl A, Soligalla RD, Reddy P, Esteban CR, Tang Fuchou*, Liu GH*, Belmonte JC*. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science 2015; 348: 1160-1163 (*: Co-corresponding authors).

  Wen L*, Tang Fuchou*, Charting a Map through the Cellular Reprogramming Landscape. Cell Stem Cell 2015; 16: 215-216 (*: Co-corresponding authors) (Preview).

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