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Single-cell atlas of the human brain vasculature across development, adulthood and disease (scRNA-Seq)

ABSTRACT: A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood. Here, we performed single-cell RNA sequencing of 606,380 freshly isolated endothelial, perivascular and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We uncover extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across eight vascular-dependent Central Nervous System (CNS) pathologies including brain tumors and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict numerous endothelial-to-perivascular cell ligand-receptor crosstalk including immune-related and angiogenic pathways, thereby unraveling a central role for the endothelium within brain neurovascular unit signaling networks. Our single-cell brain atlas provides insight into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies

ORGANISM(S): Homo sapiens

PROVIDER: GSE256490 | GEO | 2024/02/29

REPOSITORIES: GEO

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Project description:Brain perivascular cells have been recently identified as new mesodermal cell type of the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and â to a lesser extend â tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely discussed for the use in cell therapy in many neurological disorders. Therefore it is of importance to better understand the âintrinsicâ MSC population of the human brain. Here we systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells to fetal and adult human brain-derived NSCs and adult human bone marrow derived MSCs. We found that adult human brain pericytes can be isolated from hippocampal as well as cortical white matter, are â in contrast to adult human NSCs â easily expandable in monolayer cultures and show high similarities to human bone marrow-derived MSCs both regarding surface marker expression and whole transcriptome analysis. Human brain pericytes differentiated only in negligible amounts into neuroectodermal cell types using various differentiation conditions but efficiently differentiated into mesodermal progenies. Thus bone marrow-derived MSCs resemble human brain pericytes and might be therefore very interesting for possible autologous NPC-based treatment strategies, cell therapeutic approaches of neurological diseases. For the gene expression microarray analysis we used the Affymetrix U133A chips The whole procedure was performed following the manufacturer's standard protocol (Affymetrix, Santa Clara, CA). For the data processing, normalization was calculated with the GCRMA (GC content corrected Robust Multi-array Analysis) algorithm. Data post-processing and graphics was performed with in-house developed functions in Matlab. 17 samples were analyzed fNSC, Neural Stem Cell, 2 replicates ANPC-hip, adult Neuroprogenitor - Cell Hippocampus, 3 replicates ANPC-wm, adult Neuroprogenitor Cell - White Matter, 3 replicates ABPMC-hip, adult Brain Perivascular Mesodermal Cell - Hippocampus, 3 replicates ABPMC-wm, adult Brain Perivascular Mesodermal Cell - White Matter, 3 replicates MSC, Mesenchymal Stem Cell, 3 replicates

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Single-cell atlas of the human brain vasculature across development, adulthood and disease (scRNA-Seq)

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