Early Developmental Origins of Cortical Disorders Modeled in Human Neural Stem Cells.

ABSTRACT: The implications of the early phases of human telencephalic development, involving neural stem cells (NSCs), in the etiology of cortical disorders remain elusive. Here, we explored the expression dynamics of cortical and neuropsychiatric disorder-associated genes in datasets generated from human NSCs across telencephalic fate transitions in vitro and in vivo. We identified risk genes expressed in brain organizers and sequential gene regulatory networks across corticogenesis revealing disease-specific critical phases, when NSCs are more vulnerable to gene dysfunctions, and converging signaling across multiple diseases. Moreover, we simulated the impact of risk transcription factor (TF) depletions on different neural cell types spanning the developing human neocortex and observed a spatiotem

SUBMITTER: Mato-Blanco X 

PROVIDER: S-EPMC11195173 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature