PXD029526

PXD029526 is an original dataset announced via ProteomeXchange.

Title	DLG2 knockout reveals neurogenic transcriptional programs underlying neuropsychiatric disorders and cognition
Description	A complex train of events unfolds during brain development, guided by activation/repression of gene expression programs. It remains unclear how this process is disrupted in disease. Here we integrate human genetics with transcriptomic data from differentiation of human embryonic stem cells into cortical excitatory neurons. This reveals a cascade of transcriptional programs activated during early corticoneurogenesis in vitro and in vivo. Genetic variation in these programs is robustly associated with neuropsychiatric disorders and cognitive function, with variants concentrated in loss-of-function intolerant genes. Neurogenic programs also capture schizophrenia GWAS enrichment previously identified in mature excitatory neurons, suggesting that pathways activated during pre-natal development underlie disease-relevant deficits in mature neuronal function. Down-regulation of these programs in DLG2-/- lines delays expression of cell-type identity and impairs neuronal migration, morphology and action potential generation, validating predicted deficits. These data implicate specific cellular pathways underlying neurodevelopment in the aetiology of multiple neuropsychiatric disorders and cognition.
HostingRepository	PRIDE
AnnounceDate	2021-11-11
AnnouncementXML	Submission_2021-11-11_05:20:48.988.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Collins
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-02 08:31:45	ID requested
⏵ 1	2021-11-11 05:20:49	announced

Dataset with its publication pending

submitter keyword: Human, neurons, DLG2, LC-MS/MS

Mark O Collins
contact affiliation	School of Biosciences University of Sheffield United Kingdom
contact email	mark.collins@sheffield.ac.uk
lab head
Mark Collins
contact affiliation	University of Sheffield
contact email	mark.collins@sheffield.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029526
     1. Label: PRIDE project
     2. Name: DLG2 knockout reveals neurogenic transcriptional programs underlying neuropsychiatric disorders and cognition