Spatially Organized IGF1-mTOR Signaling Controls Human Forebrain Progenitor F ate Through Coordinated Transcriptional and Translational Programs.

ABSTRACT: The specification and maintenance of human forebrain neural progenitor cells (NPCs) depend on both intrinsic gene networks and spatially localized niche signals, but the interplay between these cues remains incompletely understood. Here, we identify a spatially organized, paracrine IGF1 signaling architecture that regulates human FOXG1⁺ NPCs through multilayered transcriptional and translational control. Using a pluripotent stem cell-derived forebrain model, we show that FOXG1⁺ NPCs express IGF1 receptors but lack endogenous IGF1, instead depending on neighboring epithelial-like domains that secrete IGF1. IGF1 promotes progenitor proliferation, clonal expansion, and vertical tissue growth by activating PI3K-AKT-mTOR and MEK-ERK pathways. Ribosome profiling and 5'UTR r

SUBMITTER: Lisst K 

PROVIDER: S-EPMC12635981 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature