Regionally defined proteomic profiles of human cerebral tissue and organoids reveal conserved molecular modules of neurodevelopment.
Fiche publication
Date publication
mai 2022
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BONNET Céline
Tous les auteurs :
Melliou S, Sangster KT, Kao J, Zarrei M, Lam KHB, Howe J, Papaioannou MD, Tsang QPL, Borhani OA, Sajid RS, Bonnet C, Leheup B, Shannon P, Scherer SW, Stavropoulos DJ, Djuric U, Diamandis P
Lien Pubmed
Résumé
Cerebral organoids have emerged as robust models for neurodevelopmental and pathological processes, as well as a powerful discovery platform for less-characterized neurobiological programs. Toward this prospect, we leverage mass-spectrometry-based proteomics to molecularly profile precursor and neuronal compartments of both human-derived organoids and mid-gestation fetal brain tissue to define overlapping programs. Our analysis includes recovery of precursor-enriched transcriptional regulatory proteins not found to be differentially expressed in previous transcriptomic datasets. To highlight the discovery potential of this resource, we show that RUVBL2 is preferentially expressed in the SOX2-positive compartment of organoids and that chemical inactivation leads to precursor cell displacement and apoptosis. To explore clinicopathological correlates of this cytoarchitectural disruption, we interrogate clinical datasets and identify rare de novo genetic variants involving RUVBL2 in patients with neurodevelopmental impairments. Together, our findings demonstrate how cell-type-specific profiling of organoids can help nominate previously unappreciated genes in neurodevelopment and disease.
Mots clés
CP: Neuroscience, cerebral organoids, mass spectrometry, neurodevelopment, proteomics
Référence
Cell Rep. 2022 05 24;39(8):110846