Fig. 4: SnRNA-seq reveals microglial dysfunction, mitochondrial failure and disrupted cell–cell interactions in COVID-19. | Nature Neuroscience

Fig. 4: SnRNA-seq reveals microglial dysfunction, mitochondrial failure and disrupted cell–cell interactions in COVID-19.

From: Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19

Fig. 4

a, UMAP plot of a total of 16,260 nuclei from human brain dorsal medulla samples on snRNA-seq (10×). Nuclei are colored by identified cell populations. EpCs, endothelial progenitor cells; VSMs, vascular smooth muscle cells. b, UMAP plot of microglia or macrophages (1,345 nuclei), colored by condition. c, Volcano plot showing the up- and downregulated genes in microglia or macrophages between control and COVID-19 samples. The colored genes are P < 0.05 and fold-change > 1.25. d, Total number of interactions (left) and interaction strength (right) of the inferred cell–cell communication networks from control (gray) and COVID-19 (dark green) conditions. e, Differential number of interactions (left) and differential interaction strength (right) among cell populations in the cell–cell communication network between control and COVID-19 samples. Red- and blue-colored edges represent increased or decreased signaling, respectively, in COVID-19 compared with controls. f, All significant interactions (left to right (L-R) pairs) from microglia or macrophages compared with all other cell populations. g, UMAP plot of the microglia or macrophage subset (1,345 nuclei), colored by identified subclusters (left) and UMAP plot of reactive microglia (MG), colored by condition (right). h, Key differentially expressed genes in reactive MG between COVID-19 and control conditions. The colour scale represents the average scaled gene expression. i,j, Percentage of cells positive for P2RY12 (i) and CD163 (j) in reactive MG, split by condition (P < 0.001; χ2 test). k, CD163 immunostaining clearly discriminating PVMs (arrow) from Iba1+CD163− microglia (arrowheads) in COVID-19 medulla. Note that microglial P2Y12R is still detectable to confirm microglial identity despite downregulation in vessel-associated MG, whereas PVMs are P2Y12R−. l, Quantitative assessment of MG and PVM numbers in control and COVID-19 medullary samples at sites showing average vascular or microglial pathology (avg. path) and severe pathology (sev. path) (n = 18 ROIs from 5 control patients, n = 12 ROIs from 5 COVID-19 cases with average pathology and n = 16 ROIs from 4 COVID-19 cases with severe pathology). The Kruskal–Wallis test with Dunn’s multiple-comparison test was used: bv-assoc. microglia: control versus severe pathology P < 0.0001; average pathology versus severe pathology P = 0.038; parenchymal microglia: control versus average pathology P = 0.0273, control versus severe pathology P = 0.0123; all microglia: control versus average pathology P = 0.0193; control versus severe pathology P < 0.0001; PVMs: control versus average pathology P = 0.0008; control versus severe pathology P < 0.0001. Data are presented as mean ± s.d. Scale bar, 20 µm.

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