体细胞核移植
重编程
胚泡
甲基化
细胞生物学
体细胞
生物
胚胎发生
诱导多能干细胞
胚胎干细胞
内细胞团
DNA甲基化
化学
胚胎
男科
基因表达
基因
细胞
遗传学
医学
作者
Tong Yu,Xin Qi,Ling Zhang,Ning Wei,Di Gao,Tengteng Xu,Yangyang Ma,Jason G. Knott,Anucha Sathanawongs,Zubing Cao,Yunhai Zhang
出处
期刊:Zygote
[Cambridge University Press]
日期:2021-04-23
卷期号:29 (6): 417-426
被引量:16
标识
DOI:10.1017/s0967199420000799
摘要
N6-Methyladenosine (m6A) regulates oocyte-to-embryo transition and the reprogramming of somatic cells into induced pluripotent stem cells. However, the role of m6A methylation in porcine early embryonic development and its reprogramming characteristics in somatic cell nuclear transfer (SCNT) embryos are yet to be known. Here, we showed that m6A methylation was essential for normal early embryonic development and its aberrant reprogramming in SCNT embryos. We identified a persistent occurrence of m6A methylation in embryos between 1-cell to blastocyst stages and m6A levels abruptly increased during the morula-to-blastocyst transition. Cycloleucine (methylation inhibitor, 20 mM) treatment efficiently reduced m6A levels, significantly decreased the rates of 4-cell embryos and blastocysts, and disrupted normal lineage allocation. Moreover, cycloleucine treatment also led to higher levels in both apoptosis and autophagy in blastocysts. Furthermore, m6A levels in SCNT embryos at the 4-cell and 8-cell stages were significantly lower than that in parthenogenetic activation (PA) embryos, suggesting an abnormal reprogramming of m6A methylation in SCNT embryos. Correspondingly, expression levels of m6A writers (METTL3 and METTL14) and eraser (FTO) were apparently higher in SCNT 8-cell embryos compared with their PA counterparts. Taken together, these results indicated that aberrant nuclear transfer-mediated reprogramming of m6A methylation was involved in regulating porcine early embryonic development.
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