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[Preprint]. 2023 Nov 6:2023.11.06.565899. [Version 1] doi: 10.1101/2023.11.06.565899

Figure 7: PRDD-seq further reveals the clonal topography and relatedness of excitatory and inhibitory neuron subtypes.

Figure 7:

(A-B) PRDD-seq-evaluated sSNVs across three clades in UMB4638 distribute throughout different excitatory and inhibitory subtypes, with restriction to middle- and upper-layer excitatory neurons seen in later-occurring sSNV. (A) Low-dimensional representation of the transcriptomic profiles of single neurons carrying sSNVs that were previously characterized in lineage studies of BA9 (Clade A18). Neurons were collected and analyzed with PRDD-seq were found to carry sSNVs from successive generations within Clade A (earliest, A1; latest, A5) and their marker profiles are used to project them (marked as solid points) onto a t-SNE representation of snRNA-seq data from UMB4638 and UMB4643 (Methods). Clusters of excitatory and inhibitory neuron subsets are indicated. (B) Cell type breakdown for sSNVs in A5. Ssnv A5 is found in middle- and upper-layer excitatory neurons but is mostly absent from deep layer excitatory neurons and from inhibitory neurons. (C) Example of a late-occurring A5 sSNV (A5b) that was identified in BA9 (underlined), is limited to middle-upper layer excitatory neurons, and marks a neuronal clone distributed widely (≥5.2 cm) and at ¡1% MF across frontal cortical areas. The topographic distance between the furthest sampled and detected cortical areas is a minimum total distance of 5.2 cm, but likely 6.2 cm since one cortical section was unavailable for sampling and measurement. (D) Regional presence of ultra-low mosaic sSNVs and the neuronal subtypes harboring them as assessed by MIPP-seq. PRDD-seq reveals mosaic sSNVs in UMB4638 (brown) and UMB4643 (gray) limited to BA17 (chr21:26365585, A¿G, chr16:75725649, C¿G), BA17 and BA18 (chr2:226043456, A¿G), occipital lobe (chr17:64478804, C¿T) or occipital and neighboring parietal lobe areas (chr2:29700911, G¿A). The sSNVs are mainly found in excitatory neurons, though some are found in inhibitory neurons as well consistent with a dorsal source of some inhibitory neurons 20. PRDD-seq analysis was conducted completed in single neurons isolated from BA17 from each individual.