
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.21.608971
preprint
1
Article
A molecular brain atlas reveals cellular shifts during the repair phase of stroke
Weber Rebecca Z http://orcid.org/0000-0002-6912-3573

Achon Buil Beatriz http://orcid.org/0000-0001-9731-9760

Rentsch Nora H http://orcid.org/0000-0001-5169-9550

Bosworth Allison
Zhang Mingzi
Kisler Kassandra http://orcid.org/0000-0002-4161-2498

Tackenberg Christian http://orcid.org/0000-0002-0019-3055

Zlokovic Berislav V http://orcid.org/0000-0002-6802-8232

Rust Ruslan http://orcid.org/0000-0003-3376-3453

22 8 2024
2024.08.21.608971https://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.21.608971
nihpp-2024.08.21.608971.pdf
Ischemic stroke triggers a cascade of pathological events that affect multiple cell types and often lead to incomplete functional recovery. Despite advances in single-cell technologies, the molecular and cellular responses that contribute to long-term post-stroke impairment remain poorly understood. To gain better insight into the underlying mechanisms, we generated a single-cell transcriptomic atlas from distinct brain regions using a mouse model of permanent focal ischemia at one month post-injury. Our findings reveal cell- and region-specific changes within the stroke-injured and peri-infarct brain tissue. For instance, GABAergic and glutamatergic neurons exhibited upregulated genes in signaling pathways involved in axon guidance and synaptic plasticity, and downregulated pathways associated with aerobic metabolism. Using cell-cell communication analysis, we identified increased strength in predicted interactions within stroke tissue among both neural and non-neural cells via signaling pathways such as those involving collagen, protein tyrosine phosphatase receptor, neuronal growth regulator, laminin, and several cell adhesion molecules. Furthermore, we found a strong correlation between mouse transcriptome responses after stroke and those observed in human nonfatal brain stroke lesions. Common molecular features were linked to inflammatory responses, extracellular matrix organization, and angiogenesis. Our findings provide a detailed resource for advancing our molecular understanding of stroke pathology and for discovering therapeutic targets in the repair phase of stroke recovery.
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pmc
