iPSC-Derived Cerebral Organoids Exhibit Premature Neurogenesis in PSEN1 Mutant Lines
(A and B) Depictions of the relative contribution of proliferative progenitors (FOXG1+/TUJ1−) and committed neurons (TUJ1+) within the neurogenic niches of iPSC-derived cerebral organoids. Quantifications were made from the basement membrane to the neural boundary (in micrometers) in at least two neurogenic regions per organoid. (B) is to scale, and the scale bar represents 25 μm.
(C) Quantification of the relative contribution of the neural progenitors and neurons for individual control, APP, and PSEN1 mutation lines. (C′) shows the same data grouped by genotype.
(D) Quantification of the overall size of the neurogenic regions for each line (progenitor contribution plus neural contribution). (D′) shows the same data grouped by genotype.
The number of independent organoid batches is shown within the histograms. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 via ANOVA with post hoc Tukey’s analysis, as indicated in Table S1. Ctrl1, blue circles; Ctrl2, blue squares; Ctrl3, blue triangles; Ctrl4, blue diamonds; APP V717I, purple circles; PSEN1 int4del, pink circles; PSEN1 Y115H, pink squares; PSEN1 M139V, green triangles; PSEN1 M146I, green diamonds; PSEN1 R278I, green hexagons. Error bars represent standard error of the mean.