文章基本信息

标题：Chronic stress-driven glucocorticoid receptor activation programs key cell phenotypes and functional epigenomic patterns in human fibroblasts
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作者：Calvin S. Leung ; Oksana Kosyk ; Emma M. Welter 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：9
页码：1-18
DOI：10.1016/j.isci.2022.104960
语种：English
出版社：Elsevier
摘要：SummaryChronic environmental stress can profoundly impact cell and body function. Although the underlying mechanisms are poorly understood, epigenetics has emerged as a key link between environment and health. The genomic effects of stress are thought to be mediated by the action of glucocorticoid stress hormones, primarily cortisol in humans, which act via the glucocorticoid receptor (GR). To dissect how chronic stress-driven GR activation influences epigenetic and cell states, human fibroblasts underwent prolonged exposure to physiological stress levels of cortisol and/or a selective GR antagonist. Cortisol was found to drive robust changes in cell proliferation, migration, and morphology, which were abrogated by concomitant GR blockade. The GR-driven cell phenotypes were accompanied by widespread, yet genomic context-dependent, changes in DNA methylation and mRNA expression, including gene loci with known roles in cell proliferation and migration. These findings provide insights into how chronic stress-driven functional epigenomic patterns become established to shape key cell phenotypes.Graphical abstractDisplay OmittedHighlights•Physiological stress levels of cortisol drive robust changes in key cell phenotypes•Stress-driven changes in cell phenotypes are abrogated by concomitant GR blockade•GR activation induces functional and phenotypically relevant epigenomic changesBiological sciences; Endocrinology; Molecular biology; Transcriptomics