PXD064424

PXD064424 is an original dataset announced via ProteomeXchange.

Title	Long-lasting extracellular matrix modifications reshape intestinal stem cell fate and promote chronic inflammation
Description	Tissue regeneration is viewed as a return to homeostasis, but whether the extracellular matrix (ECM) reverts during recovery from gut inflammation is unclear. Using temporal multi-omics, biomechanical profiling, and spatial fate mapping in colitis models, we showed that colonic ECM underwent lasting pathological reprogramming following inflammation, which we termed modified (mod)ECM. Characterized by collagen XVIII accumulation and immune-driven proteolysis, modECM redirected intestinal stem cells (ISCs) toward a wound-associated epithelial state with a pro-inflammatory transcriptional program. Ex vivo, modECM alone reshaped ISC fate by suppressing Wnt signaling and activating immune recruitment pathways. In vivo, modECM-rich zones sustained T cell infiltration and KRT14⁺ epithelial cell emergence from Lgr5⁺ progenitors. This aberrant epithelial program was mirrored in inflamed rectal biopsies from individuals with ulcerative colitis. Our findings redefine the ECM as a long-lived instructive compartment that encodes injury memory and promotes maladaptive regeneration, positioning it as a therapeutic target in chronic inflammatory diseases.
HostingRepository	PRIDE
AnnounceDate	2026-08-26
AnnouncementXML	Submission_2026-08-26_08:08:22.667.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD064424
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Idan Adir
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-29 11:46:48	ID requested
⏵ 1	2026-08-26 08:08:23	announced

10.1016/j.immuni.2026.07.022;

10.6019/PXD064424;

10.1016/J.IMMUNI.2026.07.022;

submitter keyword: Decellularized, IBD,ECM, modECM

Irit Sagi
contact affiliation	Department of Immunology and Regenerative Biology, The Weizmann Institute of Science
contact email	irit.sagi@weizmann.ac.il
lab head
Idan Adir
contact affiliation	The Weizmann Institute for Science
contact email	idanadir@gmail.com
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/2026/08/PXD064424

PRIDE project URI

• PRIDE
  1. PXD064424
     1. Label: PRIDE project
     2. Name: Long-lasting extracellular matrix modifications reshape intestinal stem cell fate and promote chronic inflammation