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Cited by 31COVID-19 Impact on ReproductionReproductive System and PregnancyPregnancy and preeclampsia studies

Single-cell analysis reveals transcriptomic and epigenomic impacts on the maternal–fetal interface following SARS-CoV-2 infection

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Gao, Lin, Mathur, Vrinda, Tam, Sabrina Ka Man, Zhou, Xuemeng, Cheung, Ming Fung, Chan, Lu Yan, Estrada-Gutiérrez, Guadalupe, Leung, Bo Wah +4 more·2023·Nature Cell Biology
DOI 10.1038/s41556-023-01169-xPMC PMC10344786
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Abstract

During pregnancy the maternal–fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent studies show increased incidences of adverse pregnancy outcomes in patients with COVID-19; however, the mechanism remains unclear. Here we analysed the molecular impacts of SARS-CoV-2 infection on the maternal–fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from patients with COVID-19 and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of pregnancy-specific glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced substantial changes to the epigenome and transcriptome at the maternal–fetal interface, which may be associated with pregnancy complications.

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  • LTR2B, LTR8B, and LTR10A are among over-represented LTR subfamilies in activated RT-typical enhancers and regulate genes critical in placental development.

    “These included LTR2B, LTR8B, and LTR10A, which regulate genes critical in placental development (Supplementary Fig. 8g and Supplementary Data 7)78,79.”

    From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [78]

    The Results section, “LTR8B elements function as enhancers in placental cells” (page unavailable), reports that a subset of LTR8B elements act as enhancers regulating placental genes. The passages do not establish that LTR2B or LTR10A regulate such genes, or that all three subfamilies are over-represented in activated RT-typical enhancers. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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References 76 · Cited by 31

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Authors
Gao, L., Mathur, V., Tam, S. K. M., Zhou, X., Cheung, M. F., Chan, L. Y., Estrada-Gutiérrez, G., Leung, B. W., Moungmaithong, S., Wang, C. C., Poon, L. C., & Leung, D.
Affiliations
  • Hong Kong University of Science and Technology (HK)
  • Chinese University of Hong Kong (HK)
Corresponding author
  • Poon, Liona C.
  • Leung, Danny
ORCID
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2023-07
Volume
25
Issue
7
Pages
1047-1060
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
DOI
10.1038/s41556-023-01169-x
PMC
PMC10344786
OpenAlex
W4382937105
Cited by
31
References
76
Citations by year
2026: 12 · 2025: 8 · 2024: 7 · 2023: 4
FWCI
10.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Cell Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
  • Research Grants Council, University Grants Committee (GRF16103721, CRF C5045-20EF)
  • Lo Ka Chung Charitable Foundation (Hong Kong Epigenomics Project) The Croucher Foundation
  • INPer COVID Project
  • Chinese University of Hong Kong (CUHK 2020.053)
  • The Croucher Foundation
  • Lo Ka Chung Charitable Foundation
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › COVID-19 Impact on Reproduction
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Keywords
COVID-19 pandemic, maternal-fetal interface, pregnancy complications, syncytiotrophoblast, single-nucleus transcriptomics, epigenomics, retrotransposons, pregnancy-specific glycoproteins, immune activation, angiogenesis, placenta
MeSH terms
COVID-19, SARS-CoV-2, Female, Humans, Pregnancy, Pregnancy Complications, Infectious, Epigenomics, Single-Cell Analysis, Transcriptome

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