Post-transcriptional regulation maintains neurogenic potential of human neural progenitor cells
Year: 2026
Type: article
Abstract: Increasing evidence supports important roles of post-transcriptional regulation in brain development; however, the precise mechanism remains unclear. Here, we show that Fragile X autosomal homolog 1 (FXR1), a brain-enriched RNA-binding protein (RBP), is essential for human neurogenesis. FXR1-deficient human cortical neural progenitor cells (NPCs) have reduced proliferation and impaired cell cycle exit during differentiation, leading to impaired neuronal differentiation. Transcriptomic and co-expression network analyses revealed FXR1 as an orchestrator of stage-specific gene programs driving neural differentiation. High-mobility group protein B2 (HMGB2), a master transcriptional regulator in stem cells, is a direct target of FXR1. FXR1 and HuR co-regulate HMGB2 mRNA, and their opposing actions on mRNA stability maintain the levels of HMGB2 in human NPCs. Reducing HMGB2 levels in FXR1-deficient NPCs rescues NPC proliferation and neuronal differentiation. Together, these findings establish post-transcriptional regulation as a key mechanism that maintains neurogenic potency of human NPCs.
Source: Stem Cell Reports
Institution: University of Wisconsin–Madison
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: U.S. Department of Defense, FRAXA Research Foundation, Simons Foundation, Wisconsin Alumni Research Foundation, Waisman Center, Autism Science Foundation, Simons Foundation Autism Research Initiative, Eagles Autism Foundation, National Institutes of Health, National Institute of Mental Health, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: The role of RNA binding protein in FXR1P in interneurons, Washington University Intellectual and Developmental Disabilities Research Center, IDENTIFY NEURONAL SIGNATURES THAT DISTINGUISH FXS PATIENTS WITH DISTINCT EEG PHENOTYPES, FMRP regulation of mitochondria and metabolism in mammalian brain development, Interrogate FMRP functions in primate brain development, Waisman Center Intellectual and Developmental Disabilities Research Center, Graduate Training in Molecular and Cellular Pharmacology, Characterization of Fragile X Syndrome 3D Cortical Organoids, Profiling cell type-specific ubiquitome in UBE3A mutant mice
OpenAlex ID: W7213459172