Fig. 5

Bulk RNA-seq identifies basal transcriptional differences between a vulnerable and resilient neuronal subtype, while revealing no consistent transcriptional changes following SI-AD treatment. a Timeline for bulk RNA-seq experiments examining transcriptional responses to SI-AD treatment in vulnerable (cortical inhibitory) and resilient (hypothalamic) hiPSC-neurons. DIV16 hiPSC-neurons were treated with PBS, SI-control, or SI-AD (0.5 nM) for 72 h prior to lysate collection for bulk RNA-seq. Created with BioRender.com. b Representative volcano plots showing Log(2)FC and -Log(10) adjusted P-values from bulk RNA-seq comparison between SI-AD treated (0.5 nM) and SI-control treated (equal volume) hiPSC-neurons in the iPSC0028 donor line. c Volcano plot of differentially expressed genes in PBS-treated cortical inhibitory and hypothalamic hiPSC-neurons derived from the iPSC0028 donor line. Log₂FC threshold > 1 and adj.P.val < 0.05. d Venn diagram showing the number of overlapping upregulated genes between DIV19 PBS-treated cortical inhibitory and hypothalamic hiPSC-neurons across hiPSC donor lines. e Top 25 enriched GO molecular functions for common upregulated genes in DIV19 cortical inhibitory vs hypothalamic hiPSC-neurons across hiPSC donor lines, enrichment p-value < 0.05. Count refers to the number of differentially expressed genes from each GO molecular function. Circle color represents adjusted p-value. f Top 25 enriched GO cellular compartments for common upregulated genes in DIV19 cortical inhibitory vs hypothalamic hiPSC-neurons across hiPSC donor lines, enrichment p-value < 0.05. Count refers to the number of differentially expressed genes from each GO biological process. Circle color represents adjusted p-value. g Sunburst plot of SynGO annotated cellular component synaptic genes which are upregulated in PBS-treated DIV19 cortical inhibitory vs hypothalamic hiPSC-neuron bulk RNA-seq analysis. Plot is colored by gene count per term. Gene categories mentioned in the text are outlined in yellow and labeled. h Sunburst plot of SynGO annotated biological process synaptic genes which are upregulated in PBS-treated DIV19 cortical inhibitory vs hypothalamic hiPSC-neuron bulk RNA-seq analysis. Plot is colored by gene count per term. Gene categories mentioned in the text are outlined in yellow and labeled with numbers