Human placental cytotrophoblast epigenome dynamics over gestation and alterations in placental disease.

Autor:	Zhang B; Department 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., Kim MY; Ely 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., Elliot G; Department of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA., Zhou Y; Ely 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., Zhao G; Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94115, USA., Li D; Department of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA., Lowdon RF; Department of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA., Gormley M; Ely 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., Kapidzic M; Ely 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., Robinson JF; Ely 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., McMaster MT; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94122, USA., Hong C; Brain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA., Mazor T; Brain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA., Hamilton E; Brain Tumor Research Center, Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA., Sears RL; Department of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA., Pehrsson EC; Department of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA., Marra MA; Centre 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., Jones SJM; Centre 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., Bilenky M; Centre 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., Hirst M; Centre 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., Wang T; Department of Genetics Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA. Electronic address: twang@wustl.edu., Costello JF; Brain 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., Fisher SJ; Ely 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.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2021 May 03; Vol. 56 (9), pp. 1238-1252.e5. Date of Electronic Publication: 2021 Apr 22.
DOI:	10.1016/j.devcel.2021.04.001
Abstrakt:	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. Competing Interests: Declaration of interests S.J.F. and M.M. are consultants for Novo Nordisk. The other authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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