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

Author:

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

Abstract

AbstractNeuroglia 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.

Publisher

Springer Science and Business Media LLC

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