Immune Factor, TNFα, Disrupts Human Brain Organoid Development Similar to Schizophrenia-Schizophrenia Increases Developmental Vulnerability to TNFα.

ABSTRACT: Schizophrenia (SZ) is a neurodevelopmental genetic disorder in which maternal immune activation (MIA) and increased tumor necrosis factor-α (TNF-α) may contribute. Previous studies using iPSC-derived cerebral organoids and neuronal cells demonstrated developmental malformation and transcriptional dysregulations, including TNF receptors and their signaling genes, common to SZ patients with diverse genetic backgrounds. In the present study, we examined the significance of the common TNF receptor dysregulations by transiently exposing cerebral organoids from embryonic stem cells (ESC) and from representative control and SZ patient iPSCs to TNF. In control iPSC organoids, TNF produced malformations qualitatively similar in, but generally less pronounced than, the malformations of the SZ iPSC-d

SUBMITTER: Benson CA 

PROVIDER: S-EPMC7484483 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature