Fig. 1

APOE deficiency leads to cellular composition changes in iPSC-derived cerebral organoids. a–d Parental control and isogenic APOE^−/− iPSCs were differentiated into cerebral organoids and dissociated into single cells at Day 90 for scRNA-seq analysis. Three cerebral organoids were pooled and analyzed as one sample (n = 3 samples/genotype). a t-SNE plot and cluster identification of scRNA-seq data from all samples. Cell clusters were defined based on the expression of cluster marker genes and known marker genes. ExN, excitatory neuron; RG, radial glia; InN, inhibitory neuron; IPC, intermediate progenitor cell; Astro, astrocyte; UD, undecided. b Dot plot of canonical genes to classify t-SNE clusters. Cluster identities are labeled on the left and canonical marker genes are indicated on the bottom. c Percentage of cell clusters in each cerebral organoid sample. d Comparison of the percentage of different cell types between control and APOE^−/− cerebral organoids. e–g The mRNA levels of cerebral layer markers (e; SLC17A7, TBR1, BCL11B, and SATB2), neural stem cell marker (f; SOX2) and astrocytic markers (g; S100B and GFAP) were quantified by RT-qPCR. Three cerebral organoids were pooled and analyzed as one sample (n = 6–9 samples/genotype). h Astrocyte differentiation in cerebral organoids were evaluated by S100β immunostaining (n = 4 organoids/genotype). Scale bar: 50 μm. Experiments were repeated in two independently differentiated batches (e–h). All data are expressed as mean ± SEM. Student’s t tests were performed to determine statistical significance. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001