Forebrain assembloids support the development of fast-spiking human PVALB+ cortical interneurons and uncover schizophrenia-associated defects Journal Article

  

Authors:	Walsh, R. M.; Crabtree, G. W.; Kalpana, K.; Jubierre, L.; Koo, S. Y.; Ciceri, G.; Gogos, J. A.; Kruglikov, I.; Studer, L.
Article Title:	Forebrain assembloids support the development of fast-spiking human PVALB+ cortical interneurons and uncover schizophrenia-associated defects
Abstract:	Disruption of parvalbumin positive (PVALB+) cortical interneurons is implicated in the pathogenesis of schizophrenia. However, how these defects emerge during development remains poorly understood. The protracted, postnatal maturation of PVALB+ cortical interneurons has complicated human pluripotent stem cell (hPSC)-based models for studying their role in neuropsychiatric disease. Here, we present a forebrain assembloid system yielding PVALB+ cortical interneurons that match the molecular identity and distinctive electrophysiology of primary PVALB+ interneurons. We further established a series of isogenic hPSC lines carrying structural variants associated with schizophrenia and identified variant-specific phenotypes affecting cortical interneuron migration, the molecular profile of PVALB+ cortical interneurons, and their ability to regulate cortical network activity, including γ-band oscillations. These findings offer plausible mechanisms for how the disruption of cortical interneuron development may impact schizophrenia risk and provide a human experimental platform to study PVALB+ cortical interneurons in health and disease. © 2025 The Authors
Keywords:	interneuron; schizophrenia; parvalbumin; organoid; human disease modeling; assembloid; human psc
Journal Title:	Neuron
ISSN:	0896-6273
Publisher:	Cell Press
Publication status:	Online ahead of print
Date Published:	2025-07-21
Online Publication Date:	2025-07-21
Language:	English
DOI:	10.1016/j.neuron.2025.06.017
PROVIDER:	scopus
PUBMED:	40695284
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105011276810&doi=10.1016%2fj.neuron.2025.06.017&partnerID=40&md5=595399cfdfe99b376501b331b10b45ba
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK authors are Ryan M. Walsh and Lorenz Studer -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/227513