Single-cell reanalysis characterizes an Osmr⁺ astrocyte state and predicts midkine signaling to Cox6b1⁺ glutamatergic neurons at 24 h after traumatic brain injury.

Authors

Fu Zhao, Luxi Cao, Jianan Chen, Guanglei Li, Yu Guo, Yimin Zhang, Shujun Lin

Published in

Brain research. Pages 150509. Aug 15, 2026. Epub Aug 15, 2026.

Abstract

Traumatic brain injury (TBI) remains a leading cause of mortality and long-term neurological disability worldwide. The cellular heterogeneity and intercellular communication in the injured brain remain incompletely defined, particularly the astrocyte-neuron crosstalk that could drive potential interventions.
We reanalyzed the publicly available single-cell RNA-sequencing dataset GSE290150, comprising 60,962 high-quality cells from the ipsilateral cortex of mice at 24 h after TBI or sham surgery. Integrated bioinformatic analyses, including unsupervised clustering, gene-set activity scoring, pseudotime inference, transcriptional regulatory network analysis using SCENIC, and cell-cell communication inference using CellChat, were performed to characterize the early post-TBI cellular landscape.
We identified five astrocyte subpopulations. Descriptive analysis of the pooled cells showed a greater relative proportion of C3 Osmr⁺ astrocytes in the TBI group than in the Sham group. This subpopulation exhibited a highly reactive transcriptional state with concurrent protection-associated and neurotoxicity-associated features, together with relatively high oxidative-phosphorylation- and glutamate-metabolism-related activity scores and elevated inferred Tfe3 regulon activity. Among ten neuronal subpopulations, C0 Cox6b1⁺ glutamatergic neurons displayed oxidative-phosphorylation- and aerobic-respiration-related features. CellChat analysis prioritized Mdk-Ncl as a candidate ligand-receptor interaction contributing to inferred communication from C3 Osmr⁺ astrocytes to C0 Cox6b1⁺ neurons, suggesting a potential astrocyte-to-neuron communication pattern after TBI.
This study identifies a TBI-associated C3 Osmr⁺ astrocyte subpopulation characterized by the highest pan-reactive signature together with protection-associated, neurotoxicity-associated, and metabolic gene expression features, and identifies C0 Cox6b1⁺ glutamatergic neurons as a candidate recipient population of astrocyte-derived MK signaling. Tfe3 was further prioritized as a candidate transcriptional regulator associated with the C3 Osmr⁺ astrocyte state. These findings provide a valuable framework for advancing experimental studies of astrocyte-neuron communication after TBI.

PMID:
42603599
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

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