Combined Activin A/LiCl/Noggin Treatment Improves Production of Mouse Embryonic Stem Cell-Derived Definitive Endoderm Cells
Combined Activin A/LiCl/Noggin Treatment Improves Production of Mouse Embryonic Stem Cell-Derived Definitive Endoderm Cells
复制标题
激活素 A/LiCl/Noggin 联合治疗可提高小鼠胚胎干细胞衍生的定形内胚层细胞的产生
DOI：
10.1002/jcb.22962
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发表时间：
2011-04-01
影响因子：
4
通讯作者：
Wang, Xin
中科院分区：
文献类型：
--
作者：
Li, Fuming;He, Zhiying;Wang, Xin
最终内胚层（DE）细胞的诱导是胚胎干（ES）细胞向肝或胰腺祖细胞分化的先决条件。我们建立了一种在悬浮胚体（EB）培养中诱导小鼠ES细胞来源DE细胞的有效方法。与以往的研究类似，小鼠ES细胞来源的DE细胞，定义为Cxcr4(+)c-Kit(+),Cxcr4(+)E-cadherin（+）细胞或Cxcr4(+)PDGFRa（-）细胞，可以在诱导第4天在无血清的EBs中诱导。在EBs分化过程中，Wnt、Nodal和FGF信号通路的激活促进了DE细胞的分化，而BMP4信号通路的激活则抑制了这一过程。本研究发现，LiCl化学激活典型Wnt信号通路可与Activin A介导的Nodal信号通路协同促进DE细胞的诱导，而Noggin与Activin A/LiCl共同抑制Bmp4信号通路可进一步提高DE细胞分化效率。结果表明，所获得的DE细胞具有成为肝祖细胞或胰腺祖细胞的能力。综上所述，激活素A/LiCl/Noggin联合处理显著提高了小鼠ES细胞源性DE细胞的生成效率。我们的工作将对胚胎干细胞衍生的肝细胞和胰腺细胞的产生有很大的帮助，为未来的再生医学提供依据。j .细胞。中国生物医学工程学报，2011,31(2):444 - 444。(C) 2010 Wiley-Liss, Inc。
Induction of definitive endoderm (DE) cells is a prerequisite for the whole process of embryonic stem (ES) cells differentiating into hepatic or pancreatic progenitor cells. We have established an efficient method to induce mouse ES cell-derived DE cells in suspension embryonic body (EB) culture. Similar to previous studies, mouse ES cell-derived DE cells, which were defined as Cxcr4(+)c-Kit(+),Cxcr4(+)E-cadherin(+) cells or Cxcr4(+)PDGFRa(-) cells, could be induced in the serum-free EBs at Day 4 of induction. The activations of Wnt, Nodal, and FGF signaling pathways in differentiating EBs promoted DE cell differentiation, while activation of BMP4 signaling inhibited the process. In the present study, we found that chemical activation of canonical Wnt signaling pathway by LiCl could synergize with Activin A-mediated Nodal signaling pathway to promote induction of DE cells, and inhibition of Bmp4 signaling by Noggin along with Activin A/LiCl further improved the efficiency of DE cell differentiation. The derived DE cells were proved for their capacities to become hepatic progenitor cells or pancreatic progenitor cells. In conclusion, we significantly improved the efficiency of generating mouse ES cell-derived DE cells by combined Activin A/LiCl/Noggin treatment. Our work will be greatly helpful to generate ES cell-derived hepatic cells and ES cell-derived pancreatic cells for future regenerative medicine. J. Cell. Biochem. 112: 1022-1034, 2011. (C) 2010 Wiley-Liss, Inc.