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Chunk #5 — Gene networks discriminate fetal cell types

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Transcriptional landscape of the prenatal human brain.
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To identify principal features of the developing cortical transcriptome, we performed weighted gene co-expression network analysis (WGCNA)36 on all 526 neocortical samples, and identified 42 modules of co-expressed genes (Fig. 3a; Suppl. Tables 5–6; Suppl. Methods). WGCNA clusters genes with similar expression patterns in an unbiased manner, allowing a biological interpretation of transcriptional patterns (layer, cell type, biological process, disease, etc.)23,36–38. Here, most gene clusters ("modules") corresponded to layers and/or changes with age, (Fig. 3a-b; Extended Data Fig. 4) while areal patterning appeared to be a more subtle transcriptional feature. For example, module C16 is enriched in SP (Fig. 3b, lower right), and shows hallmarks of mature neuronal function. Module C38 contains genes enriched in germinal layers, and also decreased expression with age (Fig. 3b, upper left). This module has a large signature of glia and cell division, suggesting that these genes reflect decreasing progenitor cell division. Conversely, module C22 is enriched in newly generated postmitotic neurons of the CP, and increases with age (Fig. 3b, lower left). Importantly given the small sample size, this temporal patterning in C38 and