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

Author:

Li Yanhe1,Zheng Caihong2,Liu Yingdong1,He Jincan1,Zhang Qiang3,Zhang Yalin1,Kou Xiaochen1,Zhao Yanhong1,Liu Kuisheng1,Bai Dandan1,Jia Yanping1,Han Xiaoxiao1,Sheng Yifan1,Yin Jiqing1,Wang Hong1,Gao Shuai3ORCID,Liu Wenqiang1,Gao Shaorong1ORCID

Affiliation:

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

Abstract

ABSTRACT 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 naïve-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 markedly 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.

Funder

Ministry of Science and Technology

National Natural Science Foundation of China

National Key Research and Development Program of China

China Agricultural University

Youth Innovation Promotion Association of the Chinese Academy of Sciences

Science and Technology Commission of Shanghai Municipality

Publisher

Oxford University Press (OUP)

Subject

Multidisciplinary

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3