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Dissecting signaling pathways that govern self-renewal of rabbit embryonic stem cells
Shufen Wang1,2; Yi Shen3,4; Xiaohua Yuan1,2,3; Kai Chen1,2,3; Xiangyu Guo1,2,3; Yongchang Chen1,2,3; Yuyu Niu1,2; Jian Li1; Ren-He Xu5; Xiyun Yan4; Qi Zhou6; Weizhi Ji1,2
2008-12-19
Source PublicationJournal of Biological Chemistry
ISSN00219258 1083351X
Volume283Issue:51Pages:35929-35940
Abstract

The pluripotency and self-renewal of embryonic stem cells (ESC) are regulated by a variety of cytokines/growth factors with some species differences. We reported previously that rabbit ESC (rESC) are more similar to primate ESC than to mouse ESC. However, the signaling pathways that regulate rESC self-renewal had not been identified. Here we show that inhibition of the transforming growth factor β (TGFβ), fibroblast growth factor (FGF), and canonical Wnt/β-catenin (Wnt) pathways results in enhanced differentiation of rESC accompanied by down-regulation of Smad2/3 phosphorylation and β-catenin expression and up-regulation of phosphorylation of Smad1 and β-catenin. These results imply that the TGFβ, FGF, and Wnt pathways are required for rESC self-renewal. Inhibition of the MAPK/ERK and PI3K/AKT pathways, which lie downstream of the FGF pathway, led to differentiation of rESC accompanied by down-regulation of phosphorylation of ERK1/2 or AKT, respectively. Long-term self-renewal of rESC could be achieved by adding a mixture of TGFβ ligands (activin A, Nodal, or TGFβ1) plus basic FGF (bFGF) and Noggin in the absence of serum and feeder cells. Our findings also suggest that there is a regulatory network consisting of the FGF, Wnt, and TGFβ pathways that controls rESC pluripotency and self-renewal. We conclude that bFGF controls the stem cell properties of rESC both directly and indirectly through TGFβ or other pathways, whereas the effect of Wnt on rESC might be mediated by the TGFβ pathway. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI10.1074/jbc.M804091200
URLView the original
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000261687900068
PublisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
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Cited Times [WOS]:37   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Co-First AuthorShufen Wang
Corresponding AuthorXiyun Yan; Qi Zhou; Weizhi Ji
Affiliation1.Kunming Primate Research Center and Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
2.Yunnan Key Laboratory of Animal Reproductive Biology, Kunming, Yunnan 650223, China
3.Graduate School, Chinese Academy of Sciences, Beijing 100039, China
4.National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
5.Department of Genetics and Developmental Biology and University of Connecticut Health Center for Regenerative Biology, University of Connecticut, Connecticut 06030-3301
6.Institute of Zoology, Chinese Academy of Sciences, Beijing 100108, China
Recommended Citation
GB/T 7714
Shufen Wang,Yi Shen,Xiaohua Yuan,et al. Dissecting signaling pathways that govern self-renewal of rabbit embryonic stem cells[J]. Journal of Biological Chemistry,2008,283(51):35929-35940.
APA Shufen Wang.,Yi Shen.,Xiaohua Yuan.,Kai Chen.,Xiangyu Guo.,...&Weizhi Ji.(2008).Dissecting signaling pathways that govern self-renewal of rabbit embryonic stem cells.Journal of Biological Chemistry,283(51),35929-35940.
MLA Shufen Wang,et al."Dissecting signaling pathways that govern self-renewal of rabbit embryonic stem cells".Journal of Biological Chemistry 283.51(2008):35929-35940.
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