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Combined activin A/LiCl/Noggin treatment improves production of mouse embryonic stem cell‐derived definitive endoderm cells
Author(s) -
Li Fuming,
He Zhiying,
Li Yangfang,
Liu Pingyu,
Chen Fei,
Wang Minjun,
Zhu Haiying,
Ding Xiaoyan,
Wangensteen Kirk J.,
Hu Yiping,
Wang Xin
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22962
Subject(s) - microbiology and biotechnology , noggin , embryonic stem cell , wnt signaling pathway , progenitor cell , stem cell , biology , chemistry , signal transduction , bone morphogenetic protein , biochemistry , gene
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. © 2010 Wiley‐Liss, Inc.