Nature Communications (Jul 2024)

Single-nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke in male rodents

  • Daniel Bormann,
  • Michael Knoflach,
  • Emilia Poreba,
  • Christian J. Riedl,
  • Giulia Testa,
  • Cyrille Orset,
  • Anthony Levilly,
  • Andréa Cottereau,
  • Philipp Jauk,
  • Simon Hametner,
  • Nadine Stranzl,
  • Bahar Golabi,
  • Dragan Copic,
  • Katharina Klas,
  • Martin Direder,
  • Hannes Kühtreiber,
  • Melanie Salek,
  • Stephanie zur Nedden,
  • Gabriele Baier-Bitterlich,
  • Stefan Kiechl,
  • Carmen Haider,
  • Verena Endmayr,
  • Romana Höftberger,
  • Hendrik J. Ankersmit,
  • Michael Mildner

DOI
https://doi.org/10.1038/s41467-024-50465-z
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 23

Abstract

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Abstract Neuroglia critically shape the brain´s response to ischemic stroke. However, their phenotypic heterogeneity impedes a holistic understanding of the cellular composition of the early ischemic lesion. Here we present a single cell resolution transcriptomics dataset of the brain´s acute response to infarction. Oligodendrocyte lineage cells and astrocytes range among the most transcriptionally perturbed populations and exhibit infarction- and subtype-specific molecular signatures. Specifically, we find infarction restricted proliferating oligodendrocyte precursor cells (OPCs), mature oligodendrocytes and reactive astrocytes, exhibiting transcriptional commonalities in response to ischemic injury. OPCs and reactive astrocytes are involved in a shared immuno-glial cross talk with stroke-specific myeloid cells. Within the perilesional zone, osteopontin positive myeloid cells accumulate in close proximity to CD44+ proliferating OPCs and reactive astrocytes. In vitro, osteopontin increases the migratory capacity of OPCs. Collectively, our study highlights molecular cross talk events which might govern the cellular composition of acutely infarcted brain tissue.