Open AccessSingle‐nucleus transcriptome analysis reveals disease‐ and regeneration‐associated endothelial cells in white matter vascular dementia
Author(s) -
Mitroi Daniel N.,
Tian Min,
Kawaguchi Riki,
Lowry William E.,
Carmichael S. Thomas
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17315
Subject(s) - white matter , transcriptome , biology , angiogenesis , vascular dementia , regeneration (biology) , oligodendrocyte , microbiology and biotechnology , pathology , dementia , myelin , cancer research , neuroscience , central nervous system , disease , gene expression , medicine , gene , genetics , radiology , magnetic resonance imaging
Background Vascular dementia (VaD) is the accumulation of vascular lesions in the subcortical white matter of the brain. These lesions progress and there is no direct medical therapy. Aims To determine the specific cellular responses in VaD so as to provide molecular targets for therapeutic development. Materials and Methods Single‐nucleus transcriptome analysis was performed in human periventricular white matter (PVWM) samples of VaD and normal control (NC) subjects. Results Differential analysis shows that cell type‐specific transcriptomic changes in VaD are associated with the disruption of specific biological processes, including angiogenesis, immune activation, axonal injury and myelination. Each cell type in the neurovascular unit within white matter has a specific alteration in gene expression in VaD. In a central cell type for this disease, subcluster analysis of endothelial cells (EC) indicates that VaD contains a disease‐associated EC subcluster that expresses genes associated with programmed cell death and a response to protein folding. Two other subpopulations of EC in VaD express molecular systems associated with regenerative processes in angiogenesis, and in axonal sprouting and oligodendrocyte progenitor cell maturation. Conclusion This comprehensive molecular profiling of brain samples from patients with VaD reveals previously unknown molecular changes in cells of the neurovascular niche, and an attempt at regeneration in injured white matter.