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调控成纤维细胞生长因子 8(FGF8)在鸡胚胎干细胞向精原干细胞分化中的作用。

Regulation of fibroblast growth factor 8 (FGF8) in chicken embryonic stem cells differentiation into spermatogonial stem cells.

机构信息

Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, P.R. China.

Department of Life Sciences, Imperial College London, London, UK.

出版信息

J Cell Biochem. 2018 Feb;119(2):2396-2407. doi: 10.1002/jcb.26402. Epub 2017 Oct 18.

Abstract

Fibroblast growth factors (FGFs) are essential in regulating the formation of spermatogonial stem cells (SSCs). Here, we explored the effect of FGF8 on chicken SSCs formation by knockdown or overexpression of FGF8 in chicken embryonic stem cells (ESCs) both in vitro and in vivo. Our results showed that knockdown of FGF8 could facilitate the differentiation of ESCs into SSCs, overexpression of FGF8 could promote PGCs self-renewal, inhibit SSCs formation. This study further revealed the positive correlation between the expression level of FGF8 and MAPK/ERK signal. In the absence of FGF8, the expression of downstream genes such as FGFR2, GRB2, RAS, BRAF, RAF1, and MEK2 was not maintained, while overexpressing FGF8 enhances them. Thus, our study demonstrated that FGF8 can regulate germ cell fate by modulating the dynamic equilibrium between differentiation and self-renewal, which provides a new idea for the study of germ cell regulatory network.

摘要

成纤维细胞生长因子(FGFs)在调节精原干细胞(SSCs)的形成中起着至关重要的作用。在这里,我们通过体外和体内敲低或过表达鸡胚胎干细胞(ESCs)中的 FGF8,探索了 FGF8 对鸡 SSCs 形成的影响。我们的结果表明,敲低 FGF8 可以促进 ESCs 向 SSCs 的分化,而过表达 FGF8 可以促进 PGCs 的自我更新,抑制 SSCs 的形成。这项研究进一步揭示了 FGF8 表达水平与 MAPK/ERK 信号之间的正相关关系。在没有 FGF8 的情况下,下游基因如 FGFR2、GRB2、RAS、BRAF、RAF1 和 MEK2 的表达无法维持,而过表达 FGF8 则增强了它们的表达。因此,我们的研究表明,FGF8 可以通过调节分化和自我更新之间的动态平衡来调节生殖细胞命运,为生殖细胞调控网络的研究提供了新的思路。

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