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Nat Cell Biol. 2018 Jul;20(7):847-858. doi: 10.1038/s41556-018-0123-2. Epub 2018 Jun 18.

Single-cell multi-omics sequencing of human early embryos.

Li L1,2, Guo F3, Gao Y1,2, Ren Y1,4, Yuan P1,4, Yan L1,4,5, Li R1,4, Lian Y1,4, Li J1,2,6,7, Hu B1,2, Gao J1,2, Wen L1,2, Tang F8,9,10, Qiao J11,12,13,14.

Author information

1
Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology Third Hospital, College of Life Sciences, Peking University, Beijing, China.
2
Biomedical Institute for Pioneering Investigation via Convergence, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Peking University, Beijing, China.
3
Center for Translational Medicine, Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
4
Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.
5
Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
6
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
7
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
8
Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology Third Hospital, College of Life Sciences, Peking University, Beijing, China. tangfuchou@pku.edu.cn.
9
Biomedical Institute for Pioneering Investigation via Convergence, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Peking University, Beijing, China. tangfuchou@pku.edu.cn.
10
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. tangfuchou@pku.edu.cn.
11
Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology Third Hospital, College of Life Sciences, Peking University, Beijing, China. jie.qiao@263.net.
12
Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China. jie.qiao@263.net.
13
Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China. jie.qiao@263.net.
14
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. jie.qiao@263.net.

Abstract

DNA methylation, chromatin states and their interrelationships represent critical epigenetic information, but these are largely unknown in human early embryos. Here, we apply single-cell chromatin overall omic-scale landscape sequencing (scCOOL-seq) to generate a genome-wide map of DNA methylation and chromatin accessibility at single-cell resolution during human preimplantation development. Unlike in mice, the chromatin of the paternal genome is already more open than that of the maternal genome at the mid-zygote stage in humans, and this state is maintained until the 4-cell stage. After fertilization, genes with high variations in DNA methylation, and those with high variations in chromatin accessibility, tend to be two different sets. Furthermore, 1,797 out of 5,155 (35%) widely open chromatin regions in promoters closed when transcription activity was inhibited, indicating a feedback mechanism between transcription and open chromatin maintenance. Our work paves the way for dissecting the complex, yet highly coordinated, epigenetic reprogramming during human preimplantation development.

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PMID:
29915357
DOI:
10.1038/s41556-018-0123-2
[Indexed for MEDLINE]

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