PXD036770

PXD036770 is an original dataset announced via ProteomeXchange.

Title	GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders
Description	Copy number variations at 7q11.23 cause neurodevelopmental disorders with shared and opposite manifestations. Deletion leads to Williams-Beuren syndrome (WBS), while duplication causes 7q11.23 microduplication syndrome (7Dup). Converging evidence indicates GTF2I, from the 7q11.23 locus, is a key mediator of the cognitive-behavioral phenotypes associated with WBS and 7Dup. Here we integrate molecular profiling of patient-derived cortical organoids (COs) and transgenic mouse models to dissect 7q11.23 disease mechanisms. Proteomic and transcriptomic profiling of COs revealed opposite dynamics of neural progenitor proliferation and transcriptional imbalances, leading to precocious excitatory neuron production in 7Dup. The accelerated excitatory neuron production in 7Dup COs could be rescued by GTF2I knockdown. Transgenic mice with Gtf2i duplication recapitulated early neuronal differentiation defects and ASD-like behaviors. Remarkably, inhibition of LSD1, a downstream effector of GTF2I, was sufficient to rescue ASD-like phenotypes. We propose that the GTF2I-LSD1 axis constitutes a molecular pathway amenable to therapeutic intervention.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_06:02:01.383.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	alessandro cuomo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-17 02:22:09	ID requested
⏵ 1	2024-01-26 06:02:02	announced

10.1126/sciadv.adh2726;

L, ó, pez-Tob, ó, n A, Shyti R, Villa CE, Cheroni C, Fuentes-Bravo P, Trattaro S, Caporale N, Troglio F, Tenderini E, Mihailovich M, Skaros A, Gibson WT, Cuomo A, Bonaldi T, Mercurio C, Varasi M, Osborne L, Testa G, dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders. Sci Adv, 9(48):eadh2726(2023) [pubmed]

submitter keyword: sociability, organoids, neurodevelopment, autism, GTF2I, transcriptomics

Giuseppe Testa
contact affiliation	Fondazione Human Technopole
contact email	giuseppe.testa@fht.org
lab head
alessandro cuomo
contact affiliation	IEO
contact email	alessandro.cuomo@ieo.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD036770

PRIDE project URI

• PRIDE
  1. PXD036770
     1. Label: PRIDE project
     2. Name: GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders