Ting Wang
Jun Xu
Chaoran Zhao
Haibo Li
Yao Fu
Yaxing Xu
Liangfu Xie
Jingru Zhao
Weifeng Yang
Ming Yin
Jinhua Wen
Hongkui Deng
1 Peking University Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;
2 Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, College of Life Sciences, Peking University, Beijing 100871, China;
3 The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;
4 Beijing Vitalstar Biotechnology, Beijing 100012, China
Funds: This work was supported by the National Key Research and Development Program of China (2016YFA0100100 and 2017YFA0103000), the National Natural Science Foundation of China (Grant Nos. 31730059 and 31521004), the Guangdong Innovative and Entrepreneurial Research Team Program (2014ZT05S216), the Science and Technology Planning Project of Guangdong Province, China (2014B020226001 and 2016B030232001), the Science and Technology Program of Guangzhou, China (201508020001).
Received Date: 2018-03-20
Rev Recd Date:2018-05-16
Abstract
Abstract
Recently we have established a new culture condition enabling the derivation of extended pluripotent stem (EPS) cells, which, compared to conventional pluripotent stem cells, possess superior developmental potential and germline competence. However, it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment. Here, we show that EPS cells can be robustly generated from non-permissive NOD-scid Il2rg-/- mice through de novo derivation from blastocysts. Furthermore, these cells can also be efficiently generated by chemical reprogramming from embryonic NOD-scid Il2rg-/- fibroblasts. NOD-scid Il2rg-/- EPS cells can be expanded for more than 20 passages with genomic stability and can be genetically modified through gene targeting. Notably, these cells contribute to both embryonic and extraembryonic lineages in vivo. More importantly, they can produce chimeras and integrate into the E13.5 genital ridge. Our study demonstrates the feasibility of generating EPS cells from refractory mouse strains, which could potentially be a general strategy for deriving mouse pluripotent cells. The generation of NOD-scid Il2rg-/- EPS cell lines permits sophisticated genetic modification in NOD-scid Il2rg-/- mice, which may greatly advance the optimization of humanized mouse models for biomedical applications.Keywords: extended pluripotent stem cell,
NOD-scid Il2rg-/- mice,
embryonic and extraembryonic lineages,
chemical reprogramming
PDF全文下载地址:
http://www.protein-cell.org/article/exportPdf?id=a96096a6-63dd-4519-afbc-ef8b704cc1db&language=en
