Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection

Wang, Jing1; Zhou, Cai1; Gao, Shuai2; Song, Xiuling1; Yang, Xinyan1; Fan, Jiaqi3; Ren, Shaofang1; Ma, Linzi1; Zhao, Jiexiang1; Cui, Manman1; Song, Ke1; Wang, Mei1; Li, Chaohui1; Zheng, Yi1; Luo, Fang1; Miao, Kai4; Bai, Xiaochun1; Hutchins, Andrew P.5; Li, Lin3; Chang, Gang6; Zhao, Xiao-Yang1,7,8

2022-08-12

10.1126/sciadv.abm3976

Science Advances   Impact Factor & Quartile

2375-2548

Round spermatid injection (ROSI) technique holds great promise for clinical treatment of a proportion of infertile men. However, the compromised developmental potential of ROSI embryos largely limits the clinical application, and the mechanisms are not fully understood. Here, we describe the transcriptome, chromatin accessibility, and DNA methylation landscapes of mouse ROSI embryos derived from early-stage round spermatids using a single-cell multiomics sequencing approach. By interrogating these data, we identify the reprogramming defects in ROSI embryos at the pronuclear stages, which are mainly associated with the misexpression of a cohort of minor zygotic genome activation genes. We screen a small compound, A366, that can significantly increase the developmental potential of ROSI embryos, in which A366 can partially overcome the reprogramming defects by amending the epigenetic and transcriptomic states. Collectively, our study uncovers the reprogramming defects in ROSI embryos for understanding the mechanisms underlying compromised developmental potential and offers an avenue for ROSI technique optimization.

SCI ; EI

English

NI Journal Papers

Others

National Key R&D Program of China["2017YFA0105001","2021YFA1102700","2020YFA0113200","2019YFA0801802","2020YFA0113300"] ; Natural Science Foundation of China["82071711","31671544","31970787","32170869","32070833","82101745","31970814","81901542"] ; Key Research and Development Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)[2018GZR110104002] ; Clinical Innovation Research Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)[2018GZR0201003] ; Outstanding Scholar Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)[2018GZR110102004] ; Science and Technology Projects of Guangzhou City[201904020031] ; Guangdong Natural Science Foundation[2019A1515010446] ; Natural Science Funds for Distinguished Young Scholar of Guangdong province[2022B1515020110] ; Natural Science Foundation of Shenzhen["JCYJ20210324120212033","JCYJ20180305163311448"] ; SZU Top Ranking Project[86000000210]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000841491100006

AMER ASSOC ADVANCEMENT SCIENCE

20223312585492

Alkylation ; Gene encoding

Biology:461.9 ; Chemical Reactions:802.2 ; Materials Science:951

Web of Science

1.Southern Med Univ, Sch Basic Med Sci, Dept Dev Biol, State Key Lab Organ Failure Res, Guangzhou 510515, Guangdong, Peoples R China
2.China Agr Univ, Coll Anim Sci & Technol, Key Lab Anim Genet Breeding & Reprod MARA, Natl Engn Lab Anim Breeding, Beijing 100193, Peoples R China
3.Southern Med Univ, Sch Basic Med Sci, Dept Pathophysiol, Guangdong Prov Key Lab Prote, Guangzhou 510515, Peoples R China
4.Univ Macau, Fac Hlth Sci, Ctr Precis Med Res & Training, Macau, Peoples R China
5.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518060, Guangdong, Peoples R China
6.Shenzhen Univ, Dept Biochem & Mol Biol, Hlth Sci Ctr, Shenzhen 518060, Guangdong, Peoples R China
7.Southern Med Univ, Guangdong Key Lab Construct & Detect Tissue Engn, Guangzhou 510515, Guangdong, Peoples R China
8.Guangzhou Regenerat Med & Hlth Guangdong Lab GRMH, Guangzhou 510700, Guangdong, Peoples R China

Wang, Jing,Zhou, Cai,Gao, Shuai,et al. Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection[J]. Science Advances,2022,8(32).

Wang, Jing.,Zhou, Cai.,Gao, Shuai.,Song, Xiuling.,Yang, Xinyan.,...&Zhao, Xiao-Yang.(2022).Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection.Science Advances,8(32).

Wang, Jing,et al."Single-cell multiomics sequencing reveals the reprogramming defects in embryos generated by round spermatid injection".Science Advances 8.32(2022).