PXD075756

PXD075756 is an original dataset announced via ProteomeXchange.

Title	An inflammasome-driven differentiation program in intestinal stem cells protects against Salmonella infection
Description	Intestinal stem cells (ISCs) are essential for sustaining epithelial renewal and barrier integrity, yet their role in orchestrating defense against enteric pathogens remains unclear. Here, we identify a stem cell–intrinsic immune mechanism whereby Lgr5⁺ ISCs detect intracellular Salmonella enterica and activate an inflammasome-dependent differentiation program. Using fluorescent-labeled Salmonella enterica, single-cell transcriptomics, fate mapping, organoid models, and genetic perturbations, we show that invaded ISCs undergo rapid reprogramming toward antimicrobial peptide-enriched Paneth cells via ASC (Pycard)-mediated inflammasome signaling. This fate switch enhances epithelial antimicrobial capacity and restricts pathogen persistence in the crypt. The response is Salmonella-specific and conserved in human intestinal organoids. Moreover, the invasion-associated transcriptional signature is enriched in ISCs from Crohn’s disease patients. Our findings reveal that ISCs act as active sensors of bacterial invasion and initiate epithelial remodeling through inflammasome signaling, highlighting stem cell plasticity as a frontline innate immune strategy.
HostingRepository	PRIDE
AnnounceDate	2026-04-05
AnnouncementXML	Submission_2026-04-05_07:35:31.903.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vladyslav Holiar
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Ultra

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-17 08:23:00	ID requested
⏵ 1	2026-04-05 07:35:32	announced

Dataset with its publication pending

submitter keyword: None

Moshe Biton
contact affiliation	Principal Investigator | The Ernst and Kaethe Ascher Career Development Chair | The Department of Immunology and Regenerative Biology | Weizmann-UK Building, Room 17 | Weizmann Institute of Science | Rehovot 76100, ISRAEL | Tel: +972-8-934-4937
contact email	moshe.biton@weizmann.ac.il
lab head
Vladyslav Holiar
contact affiliation	Weizmann Institute of Science
contact email	vlad.goliar@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/2026/04/PXD075756

PRIDE project URI

• PRIDE
  1. PXD075756
     1. Label: PRIDE project
     2. Name: An inflammasome-driven differentiation program in intestinal stem cells protects against Salmonella infection