Integrating single-cell and spatially resolved transcriptomic strategies to survey the astrocyte response to stroke in male mice

Erica Y. Scott, Nickie Safarian, Daniela Lozano Casasbuenas, Michael Dryden, Teodora Tockovska, Shawar Ali, Jiaxi Peng, Emerson Daniele, Isabel Nie Xin Lim, K. W. Annie Bang, Shreejoy Tripathy, Scott A. Yuzwa, Aaron R. Wheeler and Maryam Faiz ()
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Erica Y. Scott: University of Toronto
Nickie Safarian: University of Toronto
Daniela Lozano Casasbuenas: University of Toronto
Michael Dryden: University of Toronto
Teodora Tockovska: University of Toronto
Shawar Ali: University of Toronto
Jiaxi Peng: University of Toronto
Emerson Daniele: University of Toronto
Isabel Nie Xin Lim: University of Toronto
K. W. Annie Bang: Lunenfeld-Tanenbaum Research Institute, Flow Cytometry Core, Sinai Health
Shreejoy Tripathy: University of Toronto
Scott A. Yuzwa: University of Toronto
Aaron R. Wheeler: University of Toronto
Maryam Faiz: University of Toronto

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Astrocytes, a type of glial cell in the central nervous system (CNS), adopt diverse states in response to injury that are influenced by their location relative to the insult. Here, we describe a platform for spatially resolved, single-cell transcriptomics and proteomics, called tDISCO (tissue-digital microfluidic isolation of single cells for -Omics). We use tDISCO alongside two high-throughput platforms for spatial (Visium) and single-cell transcriptomics (10X Chromium) to examine the heterogeneity of the astrocyte response to a cortical ischemic stroke in male mice. We show that integration of Visium and 10X Chromium datasets infers two astrocyte populations, proximal or distal to the injury site, while tDISCO determines the spatial boundaries and molecular profiles that define these populations. We find that proximal astrocytes show differences in lipid shuttling, with enriched expression of Apoe and Fabp5. Our datasets provide a resource for understanding the roles of astrocytes in stroke and showcase the utility of tDISCO for hypothesis-driven, spatially resolved single-cell experiments.

Date: 2024
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DOI: 10.1038/s41467-024-45821-y

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