Since some of the hub genes in the yellow module (PNO1, DGCR8, VPS18, and HSPA4) are closely related to lysosomal stress granules formation under cellular stress conditions29,30, we immunostained the cerebral organoids for a stress granule marker Ras GTPase-activating protein-binding protein 1 (G3BP) in the cerebral organoids at week 12, and found an increase of G3BP-positive punctates in AD organoids (Fig. 6e). Here, PNO1 is linked to Alzheimer disease.