AUTHOR=Zhang Yi , Liu Yongqian , Meng Wei , Yu Xiaobo , Xu Xiaojun 
  
TITLE=Integrative transcriptomic analysis reveals microglial metabolic-inflammatory crosstalk of HK2–HSPA5–TNF axis after intracerebral hemorrhage
  
JOURNAL=Frontiers in Bioinformatics
  
VOLUME=Volume 5 - 2025
  
YEAR=2026
  
URL=https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2025.1740715
  
DOI=10.3389/fbinf.2025.1740715
  
ISSN=2673-7647
  
ABSTRACT=BackgroundIntracerebral hemorrhage (ICH) triggers secondary brain injury through neuroinflammation, yet the interplay between metabolic reprogramming and inflammatory responses remains poorly defined. This study investigated how glucose metabolism dysregulation contributes to neuroinflammatory pathogenesis following ICH.MethodsWe integrated transcriptomic datasets from bulk RNA sequencing (human perihematomal tissue), single-cell RNA sequencing (mouse ICH model), and spatial transcriptomics (mouse time-series). Bioinformatic analyses included differential expression screening, single-cell weighted gene co-expression network analysis, pseudotemporal trajectory reconstruction, and cell-cell communication inference to identify key metabolic-inflammation regulators and their spatiotemporal dynamics.ResultsMulti-omics convergence revealed hexokinase 2 (HK2), heat shock protein A5 (HSPA5), and tumor necrosis factor (TNF) as core regulators linking glucose metabolism to neuroinflammation. Single-cell analysis showed significant time-dependent regulation of HK2 in microglia, while spatial transcriptomics uncovered synchronized alterations of HK2, HSPA5, and TNF in perihematomal regions at day 7. Cell communication analysis highlighted enhanced microglia-to-neutrophil signaling via Tnf-Tnfrsf1b pairs, with TNF signaling identified as the most significantly upregulated pathway in ICH conditions.ConclusionOur multi-omics approach reveals coordinated dysregulation of glucose metabolism and inflammatory genes following ICH, with time-dependent HK2 regulation in microglia and synchronized transcriptional changes at day 7 representing critical events in neuroinflammatory progression. The identified gene networks and cellular communication patterns provide new insights into the metabolic-immune interface in ICH, offering potential targets for future therapeutic strategies.