PXD070101

PXD070101 is an original dataset announced via ProteomeXchange.

Title	Generation of urine-derived iPSC lines and 3D neural models from Dravet Syndrome patients reveals integrated clinical and proteomic signatures of disease severity
Description	Dravet syndrome (DS) is a rare and severe developmental epileptic encephalopathy of childhood, primarily caused by mutations in the SCN1A gene, which encodes a key sodium channel involved in neuronal excitability. Although animal models have provided valuable insights into DS pathophysiology, they fail to fully reproduce the molecular and network complexity of the human brain. Human induced pluripotent stem cell (iPSC)-derived neurons represent a promising alternative, yet conventional 2D cultures lack the structural and functional organization characteristic of neural tissues. Objectives This project aims to establish a human 3D model of Dravet syndrome using patient-derived iPSC neurospheres, in order to: Investigate the molecular correlates of clinical heterogeneity in DS. Identify proteomic signatures linked to disease severity assessed through clinical evaluation. Provide a translational platform to explore DS pathophysiology and test personalized therapeutic strategies. Methodology Urine epithelial cells from three DS patients carrying distinct SCN1A variants were reprogrammed into iPSCs, subsequently differentiated into neural stem cells, and aggregated into 3D neurospheres that recapitulate key features of neural tissue organization. Clinical severity was evaluated using the DANCE checklist, while isobaric quantitative proteomics (TMT-based) was used to characterize the molecular phenotypes and identify dysregulated pathways. Main Findings Comparative analyses revealed a strong correlation between molecular alterations and clinical severity: The cell line derived from the most severely affected patient exhibited major disruptions in cellular homeostasis, including stress and metabolic pathway deregulation. The other lines retained proteomic signatures consistent with preserved neuronal and synaptic function.
HostingRepository	PRIDE
AnnounceDate	2026-05-19
AnnouncementXML	Submission_2026-05-19_13:13:09.729.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guillaume Nugue
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; carbamoylated residue; acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-30 07:45:29	ID requested
⏵ 1	2026-05-19 13:13:10	announced

10.1111/JNC.70452;

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Neurophere,IPSC,TMT,Dravet Syndrome

Magno Rodrigues Junqueira
contact affiliation	Deparetmento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
contact email	magnojunqueira@iq.ufrj.br
lab head
Guillaume Nugue
contact affiliation	UFRJ
contact email	nugueg@me.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070101
     1. Label: PRIDE project
     2. Name: Generation of urine-derived iPSC lines and 3D neural models from Dravet Syndrome patients reveals integrated clinical and proteomic signatures of disease severity