上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (9): 1166-.doi: 10.3969/j.issn.1674-8115.2012.09.009

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胚胎干细胞或诱导性全能干细胞自我更新和分化机制研究进展

金 颖1, 任晓慧2, 刘晓帆1   

  1. 1.上海交通大学 医学院分子发育生物学研究室, 上海 200025； 2.中国科学院上海生命科学研究院/上海交通大学医学院健康科学研究所, 上海 200025
  • 出版日期:2012-09-28 发布日期:2012-09-29
  • 作者简介:金 颖（1959—）, 女, 研究员, 博士, 博士生导师, 上海交通大学医学院和中国科学院上海生命科学研究院/上海交通大学医学院健康科学研究所研究员、国家重点基础研究发展计划（“九七三”计划）首席科学家；电子信箱: yjin@sibs.ac.cn。
  • 基金资助:

    国家自然科学基金（30871257, 30730051, 30500088, 30570907, 30800660）；国家重点基础研究发展计划（2009CB941100, 2007CB947904, 2007CB948004, 2010CB945200, 2006CB943901）；上海市科委项目 （08dj1400502, 08JC1413100）；上海市教委项目（S30201）

Progression of molecular mechanisms controlling self-renewal and differentiation of embryonic stem cells or induced pluripotent stem cells

JIN Ying1, REN Xiao-hui2, LIU Xiao-fan1   

  1. 1.Molecular Development Biology Laboratory, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China；2.Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences &|Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Online:2012-09-28 Published:2012-09-29

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摘要：

“211工程”三期建设遗传发育与生殖医学重点学科建设的子项目——胚胎干细胞或诱导性全能干细胞定向分化机制的研究，在2008—2011年建立了着床后人胚胎早期发育的全基因组表达谱式；揭示了calcineurin/NFAT 信号通路对细胞谱系决定的调控机制；揭示以Oct4为核心的胚胎干细胞命运决定的分子调控机制，其中包括发现并系统研究了对胚胎干细胞自我更新起重要作用的转录因子Oct4的蛋白质翻译后修饰；揭示Oct4的重要合作蛋白Sox2的蛋白质翻译后修饰及在胚胎干细胞中的作用；发现共激活因子p300直接调控胚胎干细胞中Nanog的表达及调控机制；发现Oct4新的下游基因Stk40并揭示Stk40在胚胎干细胞中的功能及作用机制；首次提出核仁蛋白在胚胎干细胞自我更新维持中的重要作用。2011年“胚胎干细胞及早期胚胎发育的分子调控机制研究”项目获得教育部高等学校科学研究优秀成果奖——自然科学奖二等奖。

关键词: 干细胞, 机制研究, 科研成果

Abstract:

During 2008 to 2011, affiliated project of genetic development and reproductive medicine key discipline— research project on molecular mechanisms controlling self-renewal and differentiation of embryonic stem cells or induced pluripotent stem cells, which was funded by 211 Project at the third stage, had gained many results, including establishment of the profiling of human embryos during early organogenesis; discovery of calcineurin-NFAT signaling critically regulating early lineage specification in mouse embryonic stem cells and embryos. Moreover, the regulatory mechanism of Oct4-centered core transcriptional circuitry for ES cell fate decision is elucidated: investigating the posttranslational modification of key transcription factor Oct4; discovering PARP1 Poly(ADP-ribosyl)ates Sox2 to control Sox2 protein levels and FGF4 expression during embryonic stem cell differentiation; finding that coactivator p300 in mouse embryonic stem cell differentiation and nanog expression have critical roles; demonstrating that Stk40 links the pluripotency factor Oct4 to the Erk/MAPK pathway and controls extraembryonic endoderm differentiation. In addition, the project discovers that Ly-1 antibody reactive clone is an important nucleolar protein for control of self-renewal and differentiation in embryonic stem cells. In 2011, the project of “Research of embryonic stem cell and early embryonic developmental molecular mechanism” received an award from Ministry of Education of Higher Education Scientific Research for the excellent achievement, the second prize of the natural science.

Key words: stem cells, mechanism research, scientific research achievements