⮝ Full datasets listing

PXD063298

PXD063298 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA programmed decline in ribosome levels governs human early neurodevelopment
DescriptionHow reductions in ribosome biogenesis can result in tissue- and developmental-specific defects remain a mystery. Here we describe allelic variants in the ribosome biogenesis factor AIRIM/C1orf109 that are primarily associated with neurodevelopmental disorders. Using human cerebral organoids in combination with proteomic, single-cell transcriptome across multiple developmental stages, and single-organoid translatome analyses, we identify a previously unappreciated drop in protein production during early brain development. We find ribosome levels decrease during neuroepithelial differentiation, making differentiating cells particularly vulnerable to perturbations in ribosome biogenesis during this time. Reduced ribosome availability more profoundly impacts the translation of specific transcripts, disrupting both survival and cell fate commitment of transitioning neuroepithelia. Enhancing mTOR activity by both genetic and pharmacologic methods suppresses the growth and developmental defects associated with intellectual disability linked variants. This work provides further evidence for the functional importance of regulated changes in global protein synthesis capacity during cellular differentiation.
HostingRepositoryPRIDE
AnnounceDate2025-04-30
AnnouncementXMLSubmission_2025-04-30_00:50:37.122.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAndrew Lemoff
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-04-24 15:36:27ID requested
12025-04-30 00:50:37announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: TMTpro 18plex, ribosome, mTOR
Contact List
Michael Buszczak
contact affiliationDepartment of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390
contact emailmichael.buszczak@utsouthwestern.edu
lab head
Andrew Lemoff
contact affiliationUT Southwestern Medical Center
contact emailandrew.lemoff@utsouthwestern.edu
dataset submitter
Full Dataset Link List
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/2025/04/PXD063298
PRIDE project URI
Repository Record List
[ + ]