学科主题基础医学
Systematically labeling developmental stage-specific genes for the study of pancreatic beta-cell differentiation from human embryonic stem cells
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
2014-10-01
DOI10.1038/cr.2014.118
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
WOS记录号WOS:000344993300008
项目编号2012CB966401 ; 2011ZX09102-010-03 ; 2013DFG30680 ; 30830061 ; GJHS20120820102148947
资助机构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
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67221
专题北京大学基础医学院_北京大学干细胞研究中心
北京大学第三临床医学院_运动医学研究所
北京大学口腔医学院_护理部
北京大学临床肿瘤学院_胸部肿瘤外一科
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
推荐引用方式
GB/T 7714
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.
APA Liu, Haisong.,Yang, Huan.,Zhu, Dicong.,Sui, Xin.,Li, Juan.,...&Deng, Hongkui.(2014).Systematically labeling developmental stage-specific genes for the study of pancreatic beta-cell differentiation from human embryonic stem cells.CELL RESEARCH,24(10),1181-1200.
MLA Liu, Haisong,et al."Systematically labeling developmental stage-specific genes for the study of pancreatic beta-cell differentiation from human embryonic stem cells".CELL RESEARCH 24.10(2014):1181-1200.
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