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Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer

Zhaodi Liao, Jixiang Zhang, Shiyu Sun, Yuzhuo Li, Yuting Xu, Chunyang Li, Jing Cao, Yanhong Nie, Zhuoyue Niu, Jingwen Liu, Falong Lu (), Zhen Liu () and Qiang Sun ()
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Zhaodi Liao: State Key Laboratory of Neuroscience, Chinese Academy of Sciences
Jixiang Zhang: University of Chinese Academy of Sciences
Shiyu Sun: State Key Laboratory of Neuroscience, Chinese Academy of Sciences
Yuzhuo Li: State Key Laboratory of Neuroscience, Chinese Academy of Sciences
Yuting Xu: State Key Laboratory of Neuroscience, Chinese Academy of Sciences
Chunyang Li: State Key Laboratory of Neuroscience, Chinese Academy of Sciences
Jing Cao: State Key Laboratory of Neuroscience, Chinese Academy of Sciences
Yanhong Nie: State Key Laboratory of Neuroscience, Chinese Academy of Sciences
Zhuoyue Niu: University of Chinese Academy of Sciences
Jingwen Liu: University of Chinese Academy of Sciences
Falong Lu: University of Chinese Academy of Sciences
Zhen Liu: State Key Laboratory of Neuroscience, Chinese Academy of Sciences
Qiang Sun: State Key Laboratory of Neuroscience, Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Somatic cell nuclear transfer (SCNT) successfully clones cynomolgus monkeys, but the efficiency remains low due to a limited understanding of the reprogramming mechanism. Notably, no rhesus monkey has been cloned through SCNT so far. Our study conducts a comparative analysis of multi-omics datasets, comparing embryos resulting from intracytoplasmic sperm injection (ICSI) with those from SCNT. Our findings reveal a widespread decrease in DNA methylation and the loss of imprinting in maternally imprinted genes within SCNT monkey blastocysts. This loss of imprinting persists in SCNT embryos cultured in-vitro until E17 and in full-term SCNT placentas. Additionally, histological examination of SCNT placentas shows noticeable hyperplasia and calcification. To address these defects, we develop a trophoblast replacement method, ultimately leading to the successful cloning of a healthy male rhesus monkey. These discoveries provide valuable insights into the reprogramming mechanism of monkey SCNT and introduce a promising strategy for primate cloning.

Date: 2024
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DOI: 10.1038/s41467-023-43985-7

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