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[Preprint]. 2024 Jun 13:2023.01.12.523820. Originally published 2023 Jan 13. [Version 2] doi: 10.1101/2023.01.12.523820

Fig. 6. Neuronal cell types in the prefrontal cortex of control and C9orf72 ALS/FTD donors.

Fig. 6.

(a) UMAP plots of neuronal clusters. (b) Gene activity scores for marker genes of excitatory and inhibitory neurons. (c) Heatmap of gene activity scores of cortical layer specific marker genes for excitatory neurons. Axonal projection subclassification is indicated below. CPN, cortical projection neurons; GN, granule neurons; SCPN, subcortical projection neurons; CThPN, corticothalamic projection neurons. (d) Heatmap of gene activity scores of marker genes associated with inhibitory neurons of subpallial origin (top), cortical layers (middle) and subclassification (bottom). CGE, caudal ganglionic eminence; MGE, medial caudal ganglionic eminence; LGE, lateral ganglionic eminence; SST, somatostatin; RELN, reelin; NPY, neuropeptide Y; PV, parvalbumin; VIP, vasoactive intestinal peptide; NDNF, neuron-derived neurotrophic factor; CCK, cholecystokinin; nNOS, neuronal nitric oxide synthase. (e) Top: summary of cell proportion deconvolution with pTDP-43 positive and negative nuclei (n.s. not statistically significant; P≤0.05 is considered statistically significant: * P≤0.05, ** P≤0.01, *** P≤0.001, **** P≤0.0001); bottom: heatmap representation of cell proportion deconvolution data in each individual nuclear pTDP-43 positive and negative transcriptome. (f) Proportion of neuronal subtypes defined by cortical projection or developmental origins in all sample groups. (g) Volcano plots showing odds ratio (OR) and FDR computed by MASC103 for all the neuronal subtypes. Red labeled neuronal subtypes that are significantly increased or depleted in association with specific C9orf72 ALS/FTD donor groups (FDR-adjusted P < 0.05; absolute OR >0). (h) Immunostaining of human postmortem cortical tissue for the pan-neuronal marker NeuN (cyan), oligodendrocyte lineage marker OLIG2 (green), CUX2 (magenta) and DAPI in blue. (i) Gene activity score for the ITGAM and ITGB2 genes that encode the heterodimer C3 receptor. (j) Number of differential hub genes found in each module. (k) Significance of WGCNA modules with different levels of pTDP-43. (l) Gene ontology analysis of the differential hub genes in the ME1 and ME4 modules. (m) Heatmap demonstrating the average gene expression of identified hub genes in modules ME1 and ME4 across all samples from the Emory cohort.