Fig. 6: snRNAseq reveals the molecular landscape of bAVM initiation and progression. | Nature Biomedical Engineering

Fig. 6: snRNAseq reveals the molecular landscape of bAVM initiation and progression.

From: A targeted vector for brain endothelial cell gene delivery and cerebrovascular malformation modelling

Fig. 6: snRNAseq reveals the molecular landscape of bAVM initiation and progression.The alternative text for this image may have been generated using AI.

a, bAVM disease modelling and workflow of snRNAseq. An injection shown for AAV-EF1α-EGFP represents the control contralateral hemisphere, and AAV-miniBEND-Cre represents the modelling of bAVM in one hemisphere. b,c, Uniform Manifold Approximation and Projection (UMAP) plot after dimension reduction clustering analysis of single-nucleus transcriptome data from both nidus (bAVM) and control (Ctrl) regions at PID15 (b) and PID27 (c). All clusters are labelled with numeric identifiers in the graph, which correspond to cells listed here. PID15-bAVM region: neurons (clusters 1, 4, 6, 10, 14 and 18); ECs (15); microglia (0, 2, 11 and 12); astrocytes (13); oligodendrocytes (3 and 7); immune cells (8, 9 and 17); NG2 glia (8). PID15-Ctrl region: neurons (0, 2, 3, 4, 5, 7, 9, 10, 11, 12, 13, 14, 15, 16 and 22); ECs (24); microglia (6 and 17); astrocytes (21); oligodendrocytes (1 and 18); immune cells (19); NG2 glia (8). PID27-bAVM region: neurons (2, 5, 7, 12, 13, 14, 16, 17 and 20); ECs (8); microglia (0, 1 and 22); astrocytes (9); oligodendrocytes (6 and 10); immune cells (4, 11, 15 and 19); NG2 glia (3 and 21). PID27-Ctrl region: neurons (0, 3, 4, 7, 11, 12, 13, 14, 16, 17 and 22); ECs (24); microglia (2, 8 and 20); astrocytes (9); oligodendrocytes (1, 18 and 19); immune cells (6, 21 and 23); NG2 glia (10). d,g, UMAP two-dimensional plot after dimension reduction, representing the clustering of combined single-nucleus transcriptomic data from all endothelial cells in the bAVM and control regions at PID15 (d) and PID27 (g). e,h, Violin plot representing the expression level of endothelial cell gene markers (Erg, Cldn5 and Flt1) in both clusters of ECs (bAVM and Ctrl) at PID15 (e) and PID27 (h). f,i, Volcano plot representing the DEGs in endothelial cells from the bAVM lesion and control brain region at PID15 (f) and PID27 (i). Significance cut-off: |log2(fold change)| ≥1 and adjusted P ≤ 0.05. Upregulated genes highlighted: Slco2a1, Cmip, Rhoj and Tacr1 at PID15, and Slco2a1, Nav3 and Tacr1 at PID27. Downregulated genes highlighted: Slco1a4, Cxcl12, Atp10a and Adipor2 at PID15, and Slco1a4, Bsg, Slc2a1 and Slc39a10 at PID27. The two-sided Wald test was used, and P values were adjusted for multiple testing using the Benjamini–Hochberg method (Padj < 0.05). Panel a created with BioRender.com.

Back to article page