Data for: Dysregulation of mTOR signaling mediates common neurite and migration defects in both idiopathic and 16p11.2 deletion autism neural precursor cells

Autism spectrum disorder (ASD) is defined by common behavioral
characteristics, raising the possibility of shared pathogenic mechanisms.
Yet, vast clinical and etiological heterogeneity suggests personalized
phenotypes. Surprisingly, our iPSC studies find that six individuals from
two distinct ASD subtypes, idiopathic and 16p11.2 deletion, have common
reductions in neural precursor cell (NPC) neurite outgrowth and migration
even though whole genome sequencing demonstrates no genetic overlap
between the datasets. To identify signaling differences that may
contribute to these developmental defects, an unbiased
phospho-(p)-proteome screen was performed. Surprisingly, despite the
genetic heterogeneity, hundreds of shared p-peptides were identified
between autism subtypes including the mTOR pathway. mTOR signaling
alterations were confirmed in all NPCs across both ASD subtypes and mTOR
modulation rescued ASD phenotypes and reproduced autism NPC-associated
phenotypes in control NPCs. Thus, our studies demonstrate that genetically
distinct ASD subtypes have common defects in neurite outgrowth and
migration which are driven by the shared pathogenic mechanism of mTOR
signaling dysregulation.