中国科学院机构知识库网格系统: Tgf beta signaling hyperactivation-induced tumorigenicity during the derivation of neural progenitors from mouse escs

Tgf beta signaling hyperactivation-induced tumorigenicity during the derivation of neural progenitors from mouse escs

文献类型：期刊论文


	Wang, ran 3; Cai, guoqing 3; Yang, xianfa 3; Jing, naihe 4; Feng, su 4; Qian, yun 4; Cai, guoqing 4; Wang, ran 4; Yang, xianfa 4; Qiao, yunbo 1; Tang, ke 1; Chen, kun 1; Wang, xiongjun 1; Jing, naihe 2; Huang, xingxu ; Tan, fangzhi ; Yang, xianfa ; Jing, naihe 3; Feng, su 3; Qian, yun 3
Source	Journal of molecular cell biology
	2018
Volume	10 Issue:3 Pages:216-228
ISSN	1674-2788
Keyword	Embryonic stem-cells Parkinsons-disease Dopaminergic-neurons Regenerative medicine Genome modification Ips cells Culture Model Transplantation Pluripotency
DOI	10.1093/jmcb/mjy013
Subtype	Article
English Abstract	Clinical therapies of pluripotent stem cells (pscs)-based transplantation have been hindered by frequent development of teratomas or tumors in animal models and clinical patients. therefore, clarifying the mechanism of carcinogenesis in stem cell therapy is of great importance for reducing the risk of tumorigenicity. here we differentiate oct4-gfp mouse embryonic stem cells (mescs) into neural progenitor cells (npcs) and find that a minority of oct4+ cells are continuously sustained at oct4+ state. these cells can be enriched and proliferated in a standard esc medium. interestingly, the differentiation potential of these enriched cells is tightly restricted with much higher tumorigenic activity, which are thus defined as differentiation-resistant escs (dr-escs). transcriptomic and epigenomic analyses show that dr-escs are characterized by primordial germ cell-like gene signatures (dazl, rec8, stra8, blimp1, etc.) and specific epigenetic patterns distinct from mescs. moreover, the dr-escs possess germ cell potential to generate sycp3+ haploid cells and are able to reside in sperm-free spermaduct induced by busulfan. finally, we find that tgf beta signaling is overactivated in dr-escs, and inhibition of tgf beta signaling eliminates the tumorigenicity of mesc-derived npcs by inducing the full differentiation of dr-escs. these data demonstrate that these tgf beta-hyperactivated germ cell-like dr-escs are the main contributor for the tumorigenicity of escs-derived target cell therapy and that inhibition of tgf beta signaling in esc-derived npc transplantation could drastically reduce the risk of tumor development.
EISSN	1759-4685
WOS Research Area	Cell Biology
Language	英语
WOS ID	Wos:000439707300005
Citation statistics
Version	出版稿
源URL	[http://202.127.25.143/handle/331003/3489]
Collection	生化所2018年发文上海生化细胞研究所_上海生科院生化细胞研究所
Affiliation	1.Guangzhou Univ, Sch Life Sci, Precise Genome Engn Ctr, Guangzhou 510006, Guangdong, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; 3.Univ Chinese Acad Sci, Shanghai 200031, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China;
Recommended Citation GB/T 7714	Wang, Ran,Cai, Guoqing,Yang, Xianfa,et al. Tgf beta signaling hyperactivation-induced tumorigenicity during the derivation of neural progenitors from mouse escs[J]. Journal of molecular cell biology,2018,10(3):216-228.
APA	Wang, Ran.,Cai, Guoqing.,Yang, Xianfa.,Jing, Naihe.,Feng, Su.,...&Qian, Yun.(2018).Tgf beta signaling hyperactivation-induced tumorigenicity during the derivation of neural progenitors from mouse escs.Journal of molecular cell biology,10(3),216-228.
MLA	Wang, Ran,et al."Tgf beta signaling hyperactivation-induced tumorigenicity during the derivation of neural progenitors from mouse escs".Journal of molecular cell biology 10.3(2018):216-228.

入库方式： OAI收割

来源：上海生物化学与细胞生物学研究所

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