ArticleDevelopmental cell2021
Human placental cytotrophoblast epigenome dynamics over gestation and alterations in placental disease.
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In one paragraph
Article in Developmental cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 3% of its field
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Preeclampsia and its relationship to pathological brain aging.Frontiers in physiology · 2022Pooled it
- The pathophysiology of pre-eclampsia.Nature reviews. Nephrology · 2026Review
- USP22 suppresses trophoblast cell necroptosis in preeclampsia by stabilizing KAT2A-mediated histone acetylation at the SFRP1 promoter.Journal of translational medicine · 2026Article
- Review
- ToxiTaRGET: a multi-omics database for toxicant-responsive molecular targets.Nature communications · 2026Article
- The KISS1/KISS1R Axis in Human Placentation: Molecular Mechanisms and Implications for Foetal Growth Restriction and Pre-Eclampsia.International journal of molecular sciences · 2026Review
- Single-cell analysis reveals essential lncRNAs regulating human trophoblast lineage differentiation.Life medicine · 2026Article
- METTL3 safeguards cell identity and epigenome of human trophoblast stem cells.Nature communications · 2025Article
- Role of epigenetic markers in cardiovascular disease following hypertensive disorders of pregnancy.Epigenomics · 2025Review
- Placental Malperfusion Is Associated With Adverse Outcomes in Congenital Heart Disease and With Genetic Variants in Placental Developmental Pathways.Journal of the American College of Cardiology · 2025Article
- Cross-tissue molecular responses in the liver and blood after toxicant exposures.Research square · 2025Article
- Deciphering the Molecular Dialogue: Mitochondria, Epigenetics, and Extracellular Vesicles in Placental Function and Pregnancy Complications.Comprehensive Physiology · 2025Review
- History of hypertensive disorders of pregnancy and risk of Alzheimer's disease and vascular dementia.Frontiers in neuroendocrinology · 2025Review
- Epigenetic Changes Regulating Epithelial-Mesenchymal Plasticity in Human Trophoblast Differentiation.Cells · 2025Article
- Profiling (placental) DNA methylation in cell-free DNA across gestation: the Rotterdam Periconception Cohort.Molecular human reproduction · 2025Article
- Perinatal mortality and other severe adverse outcomes following planned birth at 39 weeks versus expectant management in low-risk women: a population based cohort study.EClinicalMedicine · 2025Article
- Preeclampsia as a Study Model for Aging: The Klotho Gene Paradigm.International journal of molecular sciences · 2025Review
- Article
- Review
- Cell-free placental DNA: What do we really know?PLoS genetics · 2024Review
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 2 countries.
Bo ZhangDepartment of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA; Department of Developmental Biology, Center of Regenerative Medicine, Washington University School of Medicine, St Louis, MO 63108, USA.
M Yvonne KimEly and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94115, USA; Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA; Brain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA.
GiNell ElliotDepartment of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA.
Yan ZhouEly and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94115, USA; Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA; Division of Maternal-Fetal Medicine, University of California, San Francisco, San Francisco, CA 94115, USA.
Guangfeng ZhaoCenter for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA.
Daofeng LiDepartment of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA.
Rebecca F LowdonDepartment of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA.
Matthew GormleyEly and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94115, USA; Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA; Division of Maternal-Fetal Medicine, University of California, San Francisco, San Francisco, CA 94115, USA.
Mirhan KapidzicEly and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94115, USA; Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA; Division of Maternal-Fetal Medicine, University of California, San Francisco, San Francisco, CA 94115, USA.
Joshua F RobinsonEly and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94115, USA; Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA; Division of Maternal-Fetal Medicine, University of California, San Francisco, San Francisco, CA 94115, USA.
Michael T McMasterDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94122, USA.
Chibo HongBrain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA.
Tali MazorBrain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA.
Emily HamiltonBrain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA.
Renee L SearsDepartment of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA.
Erica C PehrssonDepartment of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA.
Marco A MarraCentre for High-Throughput Biology, Department of Microbiology & Immunology, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada; Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, 675 West 10th Aven, Vancouver, BC V5Z 1L3, Canada.
Steven J M JonesCentre for High-Throughput Biology, Department of Microbiology & Immunology, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada; Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, 675 West 10th Aven, Vancouver, BC V5Z 1L3, Canada.
Misha BilenkyCentre for High-Throughput Biology, Department of Microbiology & Immunology, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada; Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, 675 West 10th Aven, Vancouver, BC V5Z 1L3, Canada.
Martin HirstCentre for High-Throughput Biology, Department of Microbiology & Immunology, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada; Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, 675 West 10th Aven, Vancouver, BC V5Z 1L3, Canada.
Ting WangDepartment of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA. Electronic address: twang@wustl.edu.
Joseph F CostelloBrain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA. Electronic address: joseph.costello@ucsf.edu.
Susan J FisherEly and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94115, USA; Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA; Division of Maternal-Fetal Medicine, University of California, San Francisco, San Francisco, CA 94115, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94122, USA. Electronic address: susan.fisher@ucsf.edu.
University of California, San Francisco · USWashington University in St. Louis · USUCSF Helen Diller Family Comprehensive Cancer Center · USCanada's Michael Smith Genome Sciences Centre · CABC Cancer Agency · CABroad Center · US
Funding
The WashU-UCSC-EBI Human Genome Reference Center."U41HG010972 · NHGRI · WASHINGTON UNIVERSITY · PI Ira M Hall, Heng Li · 2019 to 2026
$24.9MProject 4: Human Endometrial Programming for Successful ImplantationP50HD055764 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIUDICE, LINDA C · 2014 to 2022
$16.4MGENCODE: comprehensive reference genome annotation for human and mouseU24HG007234 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI Fergal James Martin · 2021 to 2026
$16.1MIntegrated Epigenetic Maps of Human Embryonic and Adult CellsU01ES017154 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COSTELLO, JOSEPH F, MARRA, MARCO ANTONIO · 2008 to 2012
$11.6MWashU-Northwestern Genomic Variation and Function Data and Administrative Coordinating CenterU24HG012070 · NHGRI · WASHINGTON UNIVERSITY · PI Ting Wang, Feng Yue · 2021 to 2026
$9.7MTHE WASHU TARGET ENVIRONMENTAL EPIGENOMICS DATA COORDINATION CENTERU24ES026699 · NIEHS · WASHINGTON UNIVERSITY · PI WANG, TING · 2016 to 2021
$5.2MRESEARCH EDUCATION PROGRAM ON COMPUTATIONAL AND STATISTICAL TOOL DEVELOPMENT FOR ADDICTION GENETICSR25DA027995 · NIDA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN, RICE, JOHN P. · 2009 to 2019
$4.3MDissecting gene dysregulation at the maternal-fetal interface in preeclampsiaR37HD076253 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FISHER, SUSAN J. · 2013 to 2022
$3.4MGlobal Analyses of the Placental Epigenome in PreeclampsiaR01HD092419 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COSTELLO, JOSEPH F · 2017 to 2021
$3.1MDECODING THE IMPACT OF TRANSPOSABLE ELEMENTS ON GENE REGULATIONR01HG007175 · NHGRI · WASHINGTON UNIVERSITY · PI WANG, TING · 2014 to 2021
$2.7MConnecting transposable elements and regulatory innovation using ENCODE dataU01HG009391 · NHGRI · WASHINGTON UNIVERSITY · PI COHEN, BARAK A, FESCHOTTE, CEDRIC · 2017 to 2021
$2.4MThe WashU 4DN Network Data Coordination and Integration CenterU01CA200060 · NCI · WASHINGTON UNIVERSITY · PI WANG, TING · 2015 to 2019
$1.9MNCI NIH HHS U01 CA200060NHGRI NIH HHS R01 HG007175NHGRI NIH HHS R01 HG007354NHGRI NIH HHS U01 HG009391NHGRI NIH HHS U24 HG007234NHGRI NIH HHS U24 HG012070NHGRI NIH HHS U41 HG010972NICHD NIH HHS P50 HD055764NICHD NIH HHS R01 HD092419NICHD NIH HHS R37 HD076253NIDA NIH HHS R25 DA027995NIEHS NIH HHS R01 ES024992NIEHS NIH HHS U01 ES017154NIEHS NIH HHS U24 ES026699
Abstract
The human placenta and its specialized cytotrophoblasts rapidly develop, have a compressed lifespan, govern pregnancy outcomes, and program the offspring's health. Understanding the molecular underpinnings of these behaviors informs development and disease. Profiling the extraembryonic epigenome and transcriptome during the 2nd and 3rd trimesters revealed H3K9 trimethylation overlapping deeply DNA hypomethylated domains with reduced gene expression and compartment-specific patterns that illuminated their functions. Cytotrophoblast DNA methylation increased, and several key histone modifications decreased across the genome as pregnancy advanced. Cytotrophoblasts from severe preeclampsia had substantially increased H3K27 acetylation globally and at genes that are normally downregulated at term but upregulated in this syndrome. In addition, some cases had an immature pattern of H3K27ac peaks, and others showed evidence of accelerated aging, suggesting subtype-specific alterations in severe preeclampsia. Thus, the cytotrophoblast epigenome dramatically reprograms during pregnancy, placental disease is associated with failures in this process, and H3K27 hyperacetylation is a feature of severe preeclampsia.
Indexed as
EpigenomeAcetylationDNA MethylationEnhancer Elements, GeneticFemaleGene Expression Regulation, DevelopmentalGestational AgeHistonesHumansLysinePlacenta DiseasesPre-EclampsiaPregnancyProtein Processing, Post-TranslationalTrophoblastsHistonesLysinechorionic villicytotrophoblastDNA methylationgestational regulationH3K27acH3K9me3histone modificationhuman placentaplacental diseasepreeclampsia
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