Extended Data Fig. 12: A key role for vascular ECs in the human brain neurovascular unit across development, adulthood and disease, highlighting MHC class II mediated interactions.
From: Single-cell atlas of the human brain vasculature across development, adulthood and disease
a,d,g, UMAP plots of endothelial and perivascular cells derived from fetal brains (40,557 cells from 7 individuals) (a), adult/control brains (80,515 cells from 6 individuals) (d) and pathological brains (Arteriovenous malformations: 12,013 cells from 3 individuals; Lower-grade glioma: 20,712 cells from 4 individuals; Glioblastoma: 22,297 cells from 5 individuals; Metastasis: 9,204 cells from 3 individuals; Meningioma: 26,916 cells from 3 individuals) (g). b,e,h, Ligand and receptor analysis of fetal brain (b), adult control brain (e), and brain pathology (h) cells using CellphoneDB. Line thickness indicates the number of interactions between cell types. Tables summarize the number of interactions for each cell type. c,f,i, Heatmaps showing the number of ligand-receptor interactions between the different cells of fetal brains (c), adult/control brains (f), and pathological brains (i) computed using CellphoneDB. j,k, Circle plot showing differential analysis of strength of ligand receptor interactions in fetal over adult/control brains (j) and pathology over adult/control brains (k), red indicating upregulation, while blue indicating downregulation. l-n, Heatmap showing overall signalling patterns of different cell types in adult control (o) and pathological (p) brains. o,p,q, Circle plots showing the strength of MHC class II signalling interactions between the different cell types of fetal brain (o), adult/control brain (p), and pathological brain (q). r-r’6 Mass cytometry (IMC) imaging of metastasis tissue sample visualizing metal-conjugated CD74, pan-HLA-DR, oligo-HLA-D, CD68, CD11b, CD4, CD8 and CD31 primary antibodies and metal-conjugated secondary stains, a subset of the antibody set (Supplementary Table 24) stains present in all images. Overlay of pseudocolor images as well as individual channels for CD74, pan-HLA-DR, oligo-HLA-D, CD68, CD11b and CD4, (white, overlap; orange, CD74; cyan, pan-HLA-DR; green, oligo-HLA-D; yellow, CD68; purple, CD11b; blue, CD4; grey, CD8; red, CD31), Scale bars = 50 μm. Shown are 8 antibodies stained for. Arrowheads identify blood vessel ECs in close contact with immune cell expressing the indicated markers in the different tissues. Arrows identify blood vessel ECs not in close contact with immune cell expressing the indicated markers.
