Inhibition of Wnt activity improves peri-implantation development of somatic cell nuclear transfer embryos  

作　　者：Yanhe Li Caihong Zheng Yingdong Liu Jincan He Qiang Zhang Yalin Zhang Xiaochen Kou Yanhong Zhao Kuisheng Liu Dandan Bai Yanping Jia Xiaoxiao Han Yifan Sheng Jiqing Yin Hong Wang Shuai Gao Wenqiang Liu Shaorong Gao 

机构地区：[1]Shanghai Key Laboratory of Maternal Fetal Medicine,Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital,Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology,Shanghai Key Laboratory of Signaling and Disease Research,Frontier Science Center for Stem Cell Research,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China [2]CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China [3]Key Laboratory of Animal Genetics,Breeding and Reproduction of the MARA,National Engineering Laboratory for Animal Breeding,College of Animal Science and Technology,China Agricultural University,Beijing 100193,China

出　　处：《National Science Review》2023年第9期157-173,共17页国家科学评论（英文版）

基　　金：supported by the Ministry of Science and Technology of China(2021YFA1102900);the National Natural Science Foundation of China(31721003,31820103009,82022027,31970814,32270909 and 32200665);supported by the National Key R&D Project of China(2020YFA0113200,2021YFC2700300 and 2018YFC1003102);the 2115 Talent Development Program of China Agricultural University(to S.G.);the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2020104);the Science and Technology Commission of Shanghai Municipality(19JC1415300 and 21JC1405500).

摘　　要：Somatic cell nuclear transfer(SCNT) can reprogram differentiated somatic cells into totipotency.Although pre-implantation development of SCNT embryos has greatly improved,most SCNT blastocysts are still arrested at the peri-implantation stage,and the underlying mechanism remains elusive.Here,we develop a 3D in vitro culture system for SCNT peri-implantation embryos and discover that persistent Wnt signals block the naive-to-primed pluripotency transition of epiblasts with aberrant H3K27me3 occupancy,which in turn leads to defects in epiblast transformation events and subsequent implantation failure.Strikingly,manipulating Wnt signals can attenuate the pluripotency transition and H3K27me3 deposition defects in epiblasts and achieve up to a 9-fold increase in cloning efficiency.Finally,single-cell RNA-seq analysis reveals that Wnt inhibition marke dly enhances the lineage developmental trajectories of SCNT blastocysts during peri-implantation development.Overall,these findings reveal diminished potentials of SCNT blastocysts for lineage specification and validate a critical peri-implantation barrier for SCNT embryos.

关 键 词：SCNT reprogramming implantation WNT naïve pluripotency primed pluripotency EPIBLAST single-cell RNA-seq epigenetic barrier 

分 类 号：R714.8[医药卫生—妇产科学]