PXD063992

PXD063992 is an original dataset announced via ProteomeXchange.

Title	SOX2 is required for foregut squamous epithelial homeostasis and lost during Barrett’s esophagus development
Description	Esophageal adenocarcinoma (EA) is increasingly common. EA is thought to arise from a precursor lesion, Barrett’s esophagus (BE), in which chronic bile and acid reflux from the stomach injures the esophagus and induces the esophageal squamous epithelium to transition to a mixed gastric and intestinal glandular mucosa. The molecular determinants driving this metaplasia are poorly understood. We established a biobank of human patient-derived BE organoids that recapitulated the molecular heterogeneity of BE. Bulk and single-cell transcriptomics, corroborated with analysis of patient tissues, pointed to BE differentiation depending on a balance between two transcription factors that govern foregut versus hindgut embryonic gastrointestinal development: SOX2 (driving esophageal and stomach differentiation) and CDX2 (driving intestinal differentiation). Using squamous-specific inducible Sox2 knockout (Krt5CreER/+; Sox2Δ/Δ;ROSA26LSLTdTomato/+) mice, we found increased basal proliferation and decreased differentiation in the foregut squamous epithelium. Remarkably, Sox2Δ/Δ mice also harbored expanded glands at the squamocolumnar junction, some of which lineage traced to Krt5-expressing cells, indicating metaplasia from squamous epithelium. CUT&RUN analysis showed SOX2 bound and promoted differentiation-associated (e.g.,Krt13) and repressed proliferation-associated (e.g., Mki67) targets. Thus, SOX2 is critical for foregut squamous epithelial differentiation and its decreased expression likely an initiating step in progression to BE and thence to EA.
HostingRepository	PRIDE
AnnounceDate	2025-06-07
AnnouncementXML	Submission_2025-06-06_23:21:43.692.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuanwei Xu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-15 13:00:13	ID requested
⏵ 1	2025-06-06 23:21:44	announced

Dataset with its publication pending

submitter keyword: Human, Spatial Proteomics, Barrett’s esophagus, Esophageal adenocarcinoma, LC-MS/MS

Ramon U Jin
contact affiliation	Washington University, St. Louis
contact email	jinr@wustl.edu
lab head
Yuanwei Xu
contact affiliation	Johns Hopkins University
contact email	yxu105@jh.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063992
     1. Label: PRIDE project
     2. Name: SOX2 is required for foregut squamous epithelial homeostasis and lost during Barrett’s esophagus development