PXD072599

PXD072599 is an original dataset announced via ProteomeXchange.

Title	Intrinsic and extrinsic mechanisms alter neural cell fate specification in EPM1 Epilepsy
Description	The extracellular milieu, including extracellular vesicles (EVs), plays a pivotal role in brain development by regulating neural processes such as proliferation, differentiation, and migration. In this study, we sought to elucidate the pathogenesis of progressive myoclonus epilepsy type 1 (EPM1), a disease caused by mutations in the CSTB gene, using cerebral organoids (COs) derived from EPM1 patient cells. The results demonstrate that EPM1 COs display increased electrophysiological activity and a disrupted excitatory/inhibitory balance. Single-cell RNA sequencing (scRNA-seq) analysis of ventral EPM1-COs revealed an abnormal specification of progenitor fate, with a shift toward dorsal neuron identities at the expense of inhibitory interneurons. In addition, pathological alterations in EV biogenesis and cargo were identified, including aberrant Sonic Hedgehog (SHH) signaling, which may disrupt cortical patterning. These findings suggest that both intrinsic progenitor identity shifts and extrinsic EV-mediated signaling contribute to EPM1 pathology. Our study highlights potential therapeutic strategies mediated by EVs as a novel approach to mitigate disease progression.
HostingRepository	PRIDE
AnnounceDate	2026-07-21
AnnouncementXML	Submission_2026-07-21_03:22:13.557.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Barbara Steigenberger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-03 09:54:46	ID requested
⏵ 1	2026-07-21 03:22:14	announced

Dataset with its publication pending

submitter keyword: cell fate/cerebral organoids/CSTB/epilepsy/extracellular vesicle/SHH

Rossella Di Giaimo
contact affiliation	Department of Biology, University of Napoli Federico II, Napoli, Italy
contact email	digiaimo@unina.it
lab head
Barbara Steigenberger
contact affiliation	MPI of Biochemistry
contact email	steigenberger@biochem.mpg.de
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/2026/07/PXD072599

PRIDE project URI

• PRIDE
  1. PXD072599
     1. Label: PRIDE project
     2. Name: Intrinsic and extrinsic mechanisms alter neural cell fate specification in EPM1 Epilepsy