Dawei Yu
Jilong Ren
Chongyang Li
Jing Wang
Guihai Feng
Xuepeng Wang
Haifeng Wan
Tianda Li
Libin Wang
Ying Zhang
Tang Hai
Wei Li
Qi Zhou
1 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;
2 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China;
3 University of Chinese Academy of Sciences, Beijing 100049, China
Funds: We thank Dr. Tianqing Li for the gift of cmESCs. We also thank Shiwen Li, Xili Zhu, Qing Meng, and Xia Yang from the Institute of Zoology, Chinese Academy of Sciences, as well as Junfeng Hao from the Institute of Biophysics, Chinese Academy of Sciences for technical assistance. This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030400 to W.L.), the National Key Research and Development Program (2016YFA0100202 and 2017YFA0104401 to T.H., 2018YFA0109701 to R.F.), the National Natural Science Foundation of China (31621004 to Q.Z. and W.L., 31571533 to H.W., and 31701286 to G.F.), and the Key Research Projects of the Frontier Science of the Chinese Academy of Sciences (QYZDY-SSWSMC002 to Q.Z.).
Received Date: 2019-08-06
Rev Recd Date:2019-10-26
Publish Date:2020-02-10
Abstract
Abstract
Blastocyst complementation by pluripotent stem cell (PSC) injection is believed to be the most promising method to generate xenogeneic organs. However, ethical issues prevent the study of human chimeras in the late embryonic stage of development. Primate embryonic stem cells (ESCs), which have similar pluripotency to human ESCs, are a good model for studying interspecies chimerism and organ generation. However, whether primate ESCs can be used in xenogenous grafts remains unclear. In this study, we evaluated the chimeric ability of cynomolgus monkey (Macaca fascicularis) ESCs (cmESCs) in pigs, which are excellent hosts because of their many similarities to humans. We report an optimized culture medium that enhanced the anti-apoptotic ability of cmESCs and improved the development of chimeric embryos, in which domesticated cmESCs (D-ESCs) injected into pig blastocysts differentiated into cells of all three germ layers. In addition, we obtained two neonatal interspecies chimeras, in which we observed tissue-specific D-ESC differentiation. Taken together, the results demonstrate the capability of D-ESCs to integrate and differentiate into functional cells in a porcine model, with a chimeric ratio of 0.001-0.0001 in different neonate tissues. We believe this work will facilitate future developments in xenogeneic organogenesis, bringing us one step closer to producing tissue-specific functional cells and organs in a large animal model through interspecies blastocyst complementation.Keywords: embryonic stem cells,
blastocyst complementation,
cynomolgus monkey,
pig,
interspecies chimera,
organ reconstruction
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