Self-renewal, Differentiation and Reprogramming of ES/iPS Cells
Lei Xiao PhD, Stem Cell bank, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031，P.R. China e-mail: leixiao@sibs.ac.cn
Abstract
Human embryonic stem cells (hESCs) are capable of unlimited proliferation and maintain pluripotency in vitro. Thus, hESCs provide potential applications in regenerative medicine and study of early human development. We find that Activin A is necessary and sufficient for the maintenance of self-renewal and pluripotency of hESCs and supports long-term feeder and serum-free growth of hESCs. We show that Activin A induces the expression of Oct4, Nanog, and FGFs and suppresses the BMP signal. Our data indicates Activin A as a key regulator in maintenance of the stemness in hESCs. We further demonstrate that the inhibition of Activin/Nodal signaling results in the loss of hESC pluripotency and trophoblast differentiation, similar toBMP4 induced trophoblast differentiation from hESCs. We found that the BMP4 trophoblast-induction effect correlates to and depends on Activin/Nodal signaling inhibition. Therefore, we conclude that Activin/Nodal signaling inhibition is essential for hESC trophoblast differentiation and that Activin/Nodal signaling is a key regulator in hESC early lineage segregation.
The rat and pig lag far behind the mouse in functional genetic studies and generation of human disease models because of the absence of functional germline-competent ES cells, which are vital in reverse genetics approach. After the first mouse embryonic stem cell lines were derived 29 years ago, many efforts were made to establish rat and pig ES cells without success. We report here the generation of rat and porcine pluripotent stem cells by reprogramming. We characterized the iPS cells from rat and pig and investigated the expression of alkaline phosphatase, SSEA1, SSEA3, SSEA4, Tra-1-60, Tra-1-81, OCT3/4, NANOG, SOX2, REX1 and CDH1. The iPS cells also expressed high level of telomerase activity. These cells could differentiate into cell types of all three germ layers in vitro and in teratomas. Our study may facilitate the establishment of embryonic stem cells from rat and pig, and these induced pluripotent stem cells may be directly used to generate precise gene-modified animals.
编辑: helen 作者:Lei Xiao PhD
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