PXD028911

PXD028911 is an original dataset announced via ProteomeXchange.

Title	Conserved proteomic programs between human cerebral tissue and organoids implicate RUVBL2 in neurodevelopment and disease
Description	Cerebral organoids have emerged as faithful humanoid avatars for modeling numerous advanced neurodevelopmental and pathological processes and additionally serve as a powerful discovery platform for less well-characterized neurobiological programs. Towards this later prospect, we leveraged mass spectrometry-based proteomics to molecularly profile precursor and more committed neural compartments of both human-derived organoids and mid-gestation fetal brain tissue to define overlapping protein-level programs. Interestingly, this included numerous precursor-enriched transcriptional regulatory proteins that were notably not found to be differentially expressed in previous transcriptomic datasets. Specifically, we show that the RuvB-like 2 (RUVBL2) AAA-type ATPase is preferentially expressed in the SOX2-positive compartment of organoids and chemical inactivation leads to precursor cell displacement and apoptosis within the more mature DCX-positive niche. To explore potential clinicopathological correlates of this disruption in organoid cytoarchitecture, we interrogated various clinical datasets, and identified de novo deletions, missense mutations and a novel recurring tandem duplication involving RUVBL2 in patients diagnosed with neurodevelopmental and autism spectrum disorders. Together, our study demonstrates how cell-type specific and phenotype-level profiling of cerebral organoids can help nominate and implicate previously unappreciated genes in neurodevelopment and disease.
HostingRepository	PRIDE
AnnounceDate	2022-04-07
AnnouncementXML	Submission_2022-04-07_04:21:36.534.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ugljesa Djuric
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	2021-10-04 04:46:03	ID requested
⏵ 1	2022-04-07 04:21:36	announced

Dataset with its publication pending

submitter keyword: Cerebral organoids, proteomics, mass spectrometry, neurodevelopment

Phedias Diamandis
contact affiliation	University Health Network, University of Toronto
contact email	p.diamandis@mail.utoronto.ca
lab head
Ugljesa Djuric
contact affiliation	Mt. Sinai Hospital
contact email	ugljesa.djuric@mail.utoronto.ca
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/2022/04/PXD028911

PRIDE project URI

• PRIDE
  1. PXD028911
     1. Label: PRIDE project
     2. Name: Conserved proteomic programs between human cerebral tissue and organoids implicate RUVBL2 in neurodevelopment and disease