Transcriptional responses of brain organoids to oxygen changes. (A) Fraction of shared differential expression effects between cell types and conditions. Sharing was assessed from mash posterior estimates of significance and effect sizes (see Methods; Supplemental Fig. S2). Stress treatments are indicated by colored bars. Cell type classification colors are detailed in panel E and Figure 1. (B) Enrichment of gene annotations among differentially expressed genes across cell types and conditions. The 39 MSigDB Hallmark gene sets with at least one significant enrichment are shown. (C) Fractional change in hypoxia-stressed fraction of each cell type after hypoxia exposure (coarse cell classification). Cells were classified as hypoxia-stressed or hyperoxia-stressed by Gruffi using a gene set derived from treatment responses shared across all cell types. Points represent individual-level fractional changes, with cell type medians shown as crosses. See also Supplemental Figure S4. (D) Distribution of cell distances to organoid perimeters measured after immunofluorescent labeling. “Unlabeled” measurements are derived from DAPI-labeled nuclei with no immunofluorescent label. Black dots represent sample means. (E) Average topic loading for each cell type and treatment condition. Topic 7 tracks hypoxia exposure, whereas other topics reflect processes found in one or several cell types.
