PXD075094

PXD075094 is an original dataset announced via ProteomeXchange.

Title	TCF4 trinucleotide repeat expansion drives distinct proteomic signatures in Fuchs endothelial corneal dystrophy
Description	The aims of this study were to use an isogenic cell model system to investigate the proteomic consequences of TCF4 trinucleotide repeat expansion in Fuchs endothelial corneal dystrophy (FECD) and to identify potential molecular pathways contributing to disease pathogenesis. We used our previously established immortalized FECD cells (iFECD) that harbor CTG repeat expansion in TCF4 and CRISPR/Cas9 genome editing to generate an isogenic counterpart (iFECD TCF4ΔCTG) in which the expansion was deleted. Comprehensive proteomic analysis was then performed using tandem mass tag (TMT)-labeled quantitative LC-MS/MS. The resulting data were subjected to differential expression analysis, functional enrichment analysis, and protein-protein interaction network construction to elucidate the molecular impact of the CTG repeat expansion. Deletion of the CTG repeat expansion significantly altered the corneal endothelial proteome, with 90 upregulated and 111 downregulated proteins (|log2 fold change| ≥ 0.5, P-value < 0.05). Functional enrichment analysis revealed that the downregulated proteins were predominantly associated with extracellular matrix organization and cell–substrate adhesion pathways, while the upregulated proteins were enriched in interferon signaling and antigen-processing pathways. The most significantly upregulated proteins included neuropilin-1, Cip1-interacting zinc finger protein, and protein-glutamine gamma-glutamyltransferase 2, while protein phosphatase 1 regulatory subunit 14C, alpha-crystallin B chain, and 14-3-3 protein sigma showed the greatest downregulation. Our findings demonstrate that TCF4 CTG repeat expansion significantly impacts the corneal endothelial proteome, particularly affecting the extracellular matrix and cell adhesion proteins that likely contribute to guttae formation. These proteomic alterations provide mechanistic insights connecting trinucleotide repeat expansion to endothelial dysfunction and suggest potential therapeutic targets for FECD.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-08_01:27:39.073.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gajanan Sathe
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-02 10:38:21	ID requested
⏵ 1	2026-06-08 01:27:40	announced

Yuasa T, Nakagawa T, Honda T, Nishiuchi G, Sato M, Tokunaga A, Nakahara M, Tourtas T, Schl, ö, tzer-Schrehardt U, Kruse F, Padmanabhan P, Chatterjee A, Sathe G, Ghose V, Janakiraman N, Koizumi N, Elchuri SV, Okumura N, TCF4 trinucleotide repeat expansion drives distinct proteomic signatures in Fuchs endothelial corneal dystrophy. Sci Rep, 16(1):(2026) [pubmed]

10.1038/s41598-026-43789-x;

submitter keyword: Retina,Fuchs endothelial corneal dystrophy (FECD) ,CTG repeat

Sailaja Elchuri, Ph.D.
contact affiliation	Department of Nanobiotechnology, Vision Research Foundation, Sankara Nethralaya, 18 College Road, Chennai, Tamil Nadu, 600 006, India.
contact email	sailaja.elchuri@gmail.com
lab head
Gajanan Sathe
contact affiliation	Centre for Targeted Protein Degradation (CeTPD) University of Dundee
contact email	gsathe001@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD075094
     1. Label: PRIDE project
     2. Name: TCF4 trinucleotide repeat expansion drives distinct proteomic signatures in Fuchs endothelial corneal dystrophy