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  3. Single-cell multi-omics profiling of human preimplantation embryos identifies cytoskeletal defects during embryonic arrest

Single-cell multi-omics profiling of human preimplantation embryos identifies cytoskeletal defects during embryonic arrest

  • Nat Cell Biol. 2024 Jan 18. doi: 10.1038/s41556-023-01328-0.
Teng Wang # 1,  Junhua Peng # 1,  Jiaqi Fan # 1,  Ni Tang # 2 3 4 5,  Rui Hua # 6,  Xueliang Zhou 2 3 4 5,  Zhihao Wang 1,  Longfei Wang 1,  Yanling Bai 2 3 4 5,  Xiaowan Quan 1,  Zimeng Wang 1,  Li Zhang 1,  Chen Luo 6,  Weiqing Zhang 6,  Xiangjin Kang 2 3 4 5,  Jianqiao Liu 2 3 4 5,  Lei Li 7 8 9 10,  Lin Li 11
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Proteomics, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, P. R. China.
  • 2 Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
  • 3 Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
  • 4 Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
  • 5 Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China.
  • 6 Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China.
  • 7 Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China. lileigo@foxmail.com.
  • 8 Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China. lileigo@foxmail.com.
  • 9 Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China. lileigo@foxmail.com.
  • 10 Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, P. R. China. lileigo@foxmail.com.
  • 11 Guangdong Provincial Key Laboratory of Proteomics, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, P. R. China. lilin2019@i.smu.edu.cn.
  • # Contributed equally.
PMID: 38238450 DOI: 10.1038/s41556-023-01328-0
Abstract

Human in vitro fertilized embryos exhibit low developmental capabilities, and the mechanisms that underlie embryonic arrest remain unclear. Here using a single-cell multi-omics sequencing approach, we simultaneously analysed alterations in the transcriptome, chromatin accessibility and the DNA methylome in human embryonic arrest due to unexplained reasons. Arrested embryos displayed transcriptome disorders, including a distorted microtubule Cytoskeleton, increased genomic instability and impaired glycolysis, which were coordinated with multiple epigenetic reprogramming defects. We identified Aurora A kinase (AURKA) repression as a cause of embryonic arrest. Mechanistically, arrested embryos induced through AURKA inhibition resembled the reprogramming abnormalities of natural embryonic arrest in terms of the transcriptome, the DNA methylome, chromatin accessibility and H3K4me3 modifications. Mitosis-independent sequential activation of the zygotic genome in arrested embryos showed that YY1 contributed to human major zygotic genome activation. Collectively, our study decodes the reprogramming abnormalities and mechanisms of human embryonic arrest and the key regulators of zygotic genome activation.

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