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

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.