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

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...

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Main Authors: Zhaodi Liao, Jixiang Zhang, Shiyu Sun, Yuzhuo Li, Yuting Xu, Chunyang Li, Jing Cao, Yanhong Nie, Zhuoyue Niu, Jingwen Liu, Falong Lu, Zhen Liu, Qiang Sun
Format: Article
Language:English
Published: Nature Portfolio 2024-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-43985-7
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author Zhaodi Liao
Jixiang Zhang
Shiyu Sun
Yuzhuo Li
Yuting Xu
Chunyang Li
Jing Cao
Yanhong Nie
Zhuoyue Niu
Jingwen Liu
Falong Lu
Zhen Liu
Qiang Sun
author_facet Zhaodi Liao
Jixiang Zhang
Shiyu Sun
Yuzhuo Li
Yuting Xu
Chunyang Li
Jing Cao
Yanhong Nie
Zhuoyue Niu
Jingwen Liu
Falong Lu
Zhen Liu
Qiang Sun
author_sort Zhaodi Liao
collection DOAJ
description 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.
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spelling doaj.art-53be2d58f0824d44ac7b8d8945e8d7362024-01-21T12:27:42ZengNature PortfolioNature Communications2041-17232024-01-0115111810.1038/s41467-023-43985-7Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transferZhaodi Liao0Jixiang Zhang1Shiyu Sun2Yuzhuo Li3Yuting Xu4Chunyang Li5Jing Cao6Yanhong Nie7Zhuoyue Niu8Jingwen Liu9Falong Lu10Zhen Liu11Qiang Sun12Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of SciencesUniversity of Chinese Academy of SciencesInstitute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of SciencesInstitute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of SciencesInstitute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of SciencesInstitute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of SciencesInstitute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of SciencesInstitute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of SciencesUniversity of Chinese Academy of SciencesUniversity of Chinese Academy of SciencesUniversity of Chinese Academy of SciencesInstitute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of SciencesInstitute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of SciencesAbstract 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.https://doi.org/10.1038/s41467-023-43985-7
spellingShingle Zhaodi Liao
Jixiang Zhang
Shiyu Sun
Yuzhuo Li
Yuting Xu
Chunyang Li
Jing Cao
Yanhong Nie
Zhuoyue Niu
Jingwen Liu
Falong Lu
Zhen Liu
Qiang Sun
Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer
Nature Communications
title Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer
title_full Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer
title_fullStr Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer
title_full_unstemmed Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer
title_short Reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer
title_sort reprogramming mechanism dissection and trophoblast replacement application in monkey somatic cell nuclear transfer
url https://doi.org/10.1038/s41467-023-43985-7
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