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	Retinoic acid maintains self-renewal of murine embryonic stem cells via a feedback mechanism
	Wang, Rong1,2,3,4,5; Liang, Ji1,2,3,4,5; Yu, Hui-Mei1,2,3,4,5; Liang, He1,2,3,4,5; Shi, Yi-Jun1,2,3,4; Yang, Huang-Tian1,2,3,4
刊名	Differentiation
	2008-11-01
卷号	76期号:9页码:931-945
关键词	Murine embryonic stem cells Retinoic acid Differentiation Self-renewal Lif Wnt/beta-catenin
ISSN号	0301-4681
DOI	10.1111/j.1432-0436.2008.00272.x
通讯作者	Yang, huang-tian(htyang@sibs.ac.cn)
英文摘要	Embryonic stem cells (escs) are pluripotent cells derived from the inner cell mass (icm) that are able to self-renew or undergo differentiation depending on a complex interplay of extracellular signals and intracellular factors. however, the feedback regulation of differentiation-dependent esc self-renewal is poorly understood. retinoic acid (ra), a derivative of vitamin a, plays a critical role in esc differentiation and embryogenesis. in the present study, we demonstrate that short-term treatment of murine (m) escs with ra during the early differentiation stage prevented spontaneous differentiation of mescs. the ra-treated cells maintained self-renewal capacity and could differentiate into neuronal cells, cardiomyocytes, and visceral endoderm cells derived from three germ layers. the differentiation-inhibitory effect of ra was mimicked by conditioned medium from ra-treated escs and was accompanied with up-regulated expression of leukemia inhibitory factor (lif), wnt3a, wnt5a, and wnt6. such ra-induced prevention of esc differentiation was attenuated by a neutralizing antibody against lif or by a specific wnt antagonist fz8-fc and was totally reversed in the presence of both of them. furthermore, knock-down of beta-catenin, a component of the wnt signaling pathway, by small interfering rna counteracted the effect of ra. in addition, ra treatment enhanced expression of endodermal markers gata4 and afp but inhibited expression of primitive ectodermal marker fgf-5 and mesodermal marker brachyury. these findings reveal a novel role of ra in esc self-renewal and provide new insight into the regulatory mechanism of differentiation-dependent self-renewal of escs, in which wnt proteins and lif induced by ra have the synergistic action. the short-term treatment of escs with ra also offers a unique model system for study of the regulatory mechanism that controls self-renewal and specific germ-layer differentiation of escs.
WOS关键词	LEUKEMIA INHIBITORY FACTOR ; BETA-CATENIN ; GENE-EXPRESSION ; MOUSE EMBRYOS ; FACTOR LIF ; DIFFERENTIATION ; PLURIPOTENCY ; HEART ; WNT ; GATA-4
WOS研究方向	Cell Biology ; Developmental Biology
WOS类目	Cell Biology ; Developmental Biology
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000260254600002
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2392645
专题	中国科学院大学
通讯作者	Yang, Huang-Tian
作者单位	1.Chinese Acad Sci, Mol Cardiol Lab, Shanghai, Peoples R China 2.Chinese Acad Sci, SIBS, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China 3.Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China 4.SJTUSM, Shanghai Stem Cell Inst, Shanghai, Peoples R China 5.CAS, Grad Sch, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Wang, Rong,Liang, Ji,Yu, Hui-Mei,et al. Retinoic acid maintains self-renewal of murine embryonic stem cells via a feedback mechanism[J]. Differentiation,2008,76(9):931-945.
APA	Wang, Rong,Liang, Ji,Yu, Hui-Mei,Liang, He,Shi, Yi-Jun,&Yang, Huang-Tian.(2008).Retinoic acid maintains self-renewal of murine embryonic stem cells via a feedback mechanism.Differentiation,76(9),931-945.
MLA	Wang, Rong,et al."Retinoic acid maintains self-renewal of murine embryonic stem cells via a feedback mechanism".Differentiation 76.9(2008):931-945.

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