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学科主题: 基础医学
题名:
Systematically labeling developmental stage-specific genes for the study of pancreatic beta-cell differentiation from human embryonic stem cells
作者: Liu, Haisong1; Yang, Huan1; Zhu, Dicong1; Sui, Xin1; Li, Juan2; Liang, Zhen1; Xu, Lei3; Chen, Zeyu4; Yao, Anzhi4; Zhang, Long5; Zhang, Xi5; Yi, Xing4; Liu, Meng1; Xu, Shiqing6; Zhang, Wenjian6; Lin, Hua7; Xie, Lan8; Lou, Jinning6; Zhang, Yong5; Xi, Jianzhong2; Deng, Hongkui1,4,9
关键词: gene labeling ; pancreatic beta cell ; directed differentiation ; embryonic stem cell ; SUSD2
刊名: CELL RESEARCH
发表日期: 2014-10-01
DOI: 10.1038/cr.2014.118
卷: 24, 期:10, 页:1181-1200
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: INSULIN-PRODUCING CELLS ; IN-VITRO ; REGENERATIVE MEDICINE ; EXPRESSION ; NEUROGENIN3 ; PROGENITORS ; ENDODERM ; GENERATION ; DERIVATION ; LINEAGE
英文摘要:

The applications of human pluripotent stem cell (hPSC)-derived cells in regenerative medicine has encountered a long-standing challenge: how can we efficiently obtain mature cell types from hPSCs? Attempts to address this problem are hindered by the complexity of controlling cell fate commitment and the lack of sufficient developmental knowledge for guiding hPSC differentiation. Here, we developed a systematic strategy to study hPSC differentiation by labeling sequential developmental genes to encompass the major developmental stages, using the directed differentiation of pancreatic beta cells from hPSCs as a model. We therefore generated a large panel of pancreas-specific mono-and dual-reporter cell lines. With this unique platform, we visualized the kinetics of the entire differentiation process in real time for the first time by monitoring the expression dynamics of the reporter genes, identified desired cell populations at each differentiation stage and demonstrated the ability to isolate these cell populations for further characterization. We further revealed the expression profiles of isolated NGN3-eGFP(+) cells by RNA sequencing and identified sushi domain-containing 2 (SUSD2) as a novel surface protein that enriches for pancreatic endocrine progenitors and early endocrine cells both in human embryonic stem cells (hESC)-derived pancreatic cells and in the developing human pancreas. Moreover, we captured a series of cell fate transition events in real time, identified multiple cell subpopulations and unveiled their distinct gene expression profiles, among heterogeneous progenitors for the first time using our dual reporter hESC lines. The exploration of this platform and our new findings will pave the way to obtain mature beta cells in vitro.

语种: 英语
所属项目编号: 2012CB966401 ; 2011ZX09102-010-03 ; 2013DFG30680 ; 30830061 ; GJHS20120820102148947
项目资助者: National Basic Research Program of China (973 program) ; Key New Drug Creation and Manufacturing Program ; Ministry of Science and Technology ; National Natural Science Foundation of China ; Ministry of Education of China (111 project) ; National Science and Technology Major Projects Supporting Program from Shenzhen
WOS记录号: WOS:000344993300008
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67221
Appears in Collections:基础医学院_北京大学干细胞研究中心_期刊论文

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作者单位: 1.Peking Univ, Shenzhen Grad Sch, Key Lab Chem Genom, Shenzhen Stem Cell Engn Lab, Shenzhen 518055, Guangdong, Peoples R China
2.Peking Univ, Coll Engn, Dept Biomed Engn, Beijing 100871, Peoples R China
3.Acad Mil Med Sci, Hosp 307, Dept Hematopoiet Stem Cell Transplantat, Beijing 100071, Peoples R China
4.Peking Univ, Peking Tsinghua Ctr Life Sci, Coll Life Sci, MOE Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China
5.China Japan Friendship Hosp, Inst Clin Med Sci, Beijing 100029, Peoples R China
6.China Japan Friendship Hosp, Dept Gynecol & Obstet, Beijing 100029, Peoples R China
7.Beijing Renhe Hosp, Dept Gynecol & Obstet, Beijing 102600, Peoples R China
8.Peking Univ, Stem Cell Res Ctr, Dept Cell Biol, Sch Basic Med Sci,Hlth Sci Ctr, Beijing 100191, Peoples R China
9.BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China

Recommended Citation:
Liu, Haisong,Yang, Huan,Zhu, Dicong,et al. Systematically labeling developmental stage-specific genes for the study of pancreatic beta-cell differentiation from human embryonic stem cells[J]. CELL RESEARCH,2014,24(10):1181-1200.
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