Dynamic changes in chromatin accessibility within one month of mouse intracerebral hemorrhage

Summary: Intracerebral hemorrhage (ICH) is a severe stroke subtype associated with high mortality and disability. Understanding the molecular and cellular mechanisms behind ICH is vital for developing effective therapeutic interventions. We utilized a single-nucleus assay for transposase-accessible...

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Main Authors: Rong Xiang, Kang OuYang, Junmin Wang, Zhan Chen, Jin Tao, Xinru Zhang, Houlian Zhang, Zhiyun Li, Luyao Wang, Ruoqi Ding, Chuanyu Liu, Jun Xie, Yong Hou, Jian Wang, Longqi Liu, Mingyue Wang
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225010764
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Summary:Summary: Intracerebral hemorrhage (ICH) is a severe stroke subtype associated with high mortality and disability. Understanding the molecular and cellular mechanisms behind ICH is vital for developing effective therapeutic interventions. We utilized a single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) to profile changes in chromatin accessibility over the first month following ICH in murine models. We examined 262,506 cells, identifying 77,978 upregulated and 35,023 downregulated candidate cis-regulatory elements (cCREs) across days 1, 3, 7, 14, and 28. Our results revealed disruptions in multiple super-enhancers in microglia and macrophages, along with a transition of reactive astrocytes from a protective to a neurotoxic state. We also observed a significant upregulation of genes involved in hypoxia response and lipid metabolism within the remyelination pathways post-ICH. This study provides crucial insights into the epigenetic changes that occur following ICH, laying a solid foundation for future research and potential therapeutic interventions.
ISSN:2589-0042