snRNA-seq reveals key transcription factors in the inflammatory response of microglia after intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a severe neurological disease with limited treatment options. Microglia, the primary immune cells of the brain, contribute significantly to secondary injury following ICH, exhibiting heterogeneity in response across different stages of ICH. However, the exact mechanisms regulating this process remain incompletely elucidated. In this study, we utilized single-nucleus RNA sequencing (snRNA-seq) in conjunction with the ICH model of mice to establish a comprehensive single-nucleus transcriptomic atlas for ICH and further elucidate its pathogenesis to identify potential therapeutic targets. We identified five principal brain clusters with cell-type specific gene expression patterns. Focused on microglia and inflammation-associated subgroup, we identified 8 distinct microglia subtypes and the key transcription factors (TFs) involved in the inflammatory response of microglia following ICH, including Stat2, Stat1, Irf7, Nfkb1, Etv6, Cebpb, Batf, and Bach1. Notably, Stat2 and Stat1 were identified as the most central TFs. In vitro experiments revealed that inhibiting Stat2 and Stat1 can attenuate the inflammatory response in microglia after ICH. Overall, our findings enhance the understanding of cell responses in ICH and highlight potential therapeutic targets, specifically suggesting that inhibiting STAT1 and STAT2 could mitigate microglial-mediated inflammation in ICH.