Fig. 4: Transcriptomic inference of regulatory biology in germinal matrix gIPC subtypes.
From: An atlas of late prenatal human neurodevelopment resolved by single-nucleus transcriptomics
a UMAP plot of the subclustered germinal matrix analysis (from Fig. 2a) highlighting gIPC-O and gIPC-A subpopulations. b Volcano plot of DEGs between gIPC-O and gIPC-A (two-sided Wilcoxon Rank Sum test; p-adj. <0.05, average log2(fold change) > −0.5 or < −0.5). c Curated list of enriched terms computed from the top 100 gIPC-A (right) and gIPC-O (left) DEGs. Benjamini-Hochberg corrected p-adj <0.05. All terms are shown in Supplementary Data 10–11. d Schematic of the SCENIC regulon analysis. Regulons are composed of transcription factor regulators (TF1-2 on diagram) and their inferred gene targets (gA-F), namely co-expressed genes showing significant enrichment for the regulator’s binding motif. e Heatmap of the average regulon activity z-score per cell subset. f, h Predicted ZEB1 (f) and FOXO1 (h) regulon networks from (e). g, i Venn diagrams quantifying the intersection of gIPC-O DEGs and ZEB1 regulon genes (g) and of gIPC-A DEGs and FOXO1 regulon genes (i). Below are biological processes and signaling pathways related to intersection genes. Source data for (b, c, g, and i) are provided as a Source Data file. j Single z-plane immunofluorescence images showing frequent colocalization of ZEB1 (red) with gIPC marker EGFR (yellow) (arrowheads) in oSVZ an IZ regions of a third trimester tissue sample (30gw). Images (right) show magnified inset of the area bordered in the oSVZ (top left). Immunofluorescence experiments in (j–k) were repeated three independent times, with similar results. Scale bar = 50 µm. RG radial glia, oRG outer radial glia, tRG truncated radial glia, EPD ependymal cell, AC astrocyte, gIPC glial intermediate progenitor cell, OPC oligodendrocyte progenitor cell, preOL premyelinating/early myelinating BCAS1+ oligodendrocyte, nIPC neuronal intermediate progenitor cell, mIPC multipotent intermediate progenitor cell EN excitatory neuron, CPN cortical projection neuron, SPN subplate neuron, CRN Cajal Retzius cell, IN interneuron, MG microglia, CP choroid plexus, oSVZ outer subventricular zone, IZ intermediate zone, TF transcription factor, gw gestational weeks.
