{"id":"doi:10.1038/s41467-021-23113-z","kind":"article","title":"16p11.2 deletion is associated with hyperactivation of human iPSC-derived dopaminergic neuron networks and is rescued by RHOA inhibition in vitro","authors":["Sundberg M","Pinson H","Smith RS","Winden KD","Venugopal P","Tai DJC","Gusella JF","Talkowski ME","Walsh CA","Tegmark M","Sahin M"],"author_count":11,"year":2021,"published":"2021-05-18","venue":"Nature communications","cited_by":51,"doi":"10.1038/s41467-021-23113-z","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41467-021-23113-z","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41467-021-23113-z","updated":null,"pmid":"34006844","pmcid":"PMC8131375","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC8131375/pdf","abstract":"Reciprocal copy number variations (CNVs) of 16p11.2 are associated with a wide spectrum of neuropsychiatric and neurodevelopmental disorders. Here, we use human induced pluripotent stem cells (iPSCs)-derived dopaminergic (DA) neurons carrying CNVs of 16p11.2 duplication (16pdup) and 16p11.2 deletion (16pdel), engineered using CRISPR-Cas9. We show that 16pdel iPSC-derived DA neurons have increased soma size and synaptic marker expression compared to isogenic control lines, while 16pdup iPSC-derived DA neurons show deficits in neuronal differentiation and reduced synaptic marker expression. The 16pdel iPSC-derived DA neurons have impaired neurophysiological properties. The 16pdel iPSC-derived DA neuronal networks are hyperactive and have increased bursting in culture compared to controls. We also show that the expression of RHOA is increased in the 16pdel iPSC-derived DA neurons and that treatment with a specific RHOA-inhibitor, Rhosin, rescues the network activity of the 16pdel iPSC-derived DA neurons. Our data suggest that 16p11.2 deletion-associated iPSC-derived DA neuron hyperactivation can be rescued by RHOA inhibition.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"16p11.2 deletion is associated with hyperactivation of human iPSC-derived dopaminergic neuron networks and is rescued by RHOA inhibition in vitro\" by Sundberg M, Pinson H, Smith RS et al., https://doi.org/10.1038/s41467-021-23113-z, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-cell-therapy","name":"Gene & Cell Therapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}