PXD040152

PXD040152 is an original dataset announced via ProteomeXchange.

Title	ADAMTS12 serves as a checkpoint in fibrosis that controls migration and expansion of injury-responsive fibroblasts
Description	Fibrosis represents the uncontrolled replacement of parenchymal tissue with extracellular matrix (ECM) produced by myofibroblasts. While genetic fate-tracing and single-cell RNA-sequencing (scRNA-seq) technologies have helped elucidate fibroblast heterogeneity and ontogeny beyond fibroblast to myofibroblast differentiation, the novel identified fibroblast populations remain ill-defined, both in respect to the molecular cues driving their differentiation, and their subsequent role in fibrosis. Here we identify the metalloprotease ADAMTS12 in an unbiased manner as a fibroblast-specific gene that is strongly upregulated during fibrogenesis in mice and humans. In vivo knockout studies in mice confirmed that Adamts12 is critical during fibrogenesis in heart and kidney. Leveraging spatial transcriptomics, CRISPR-Cas9 gene editing and expression of catalytically active or inactive ADAMTS12 we demonstrate that the protease domain of Adamts12 controls fibrogenesis by licensing expansion and migration of a distinct fibroblast subset defined by Mt1 gene expression and strong JAK-STAT signaling.
HostingRepository	PRIDE
AnnounceDate	2024-07-01
AnnouncementXML	Submission_2024-07-01_13:38:05.136.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-16 07:58:52	ID requested
⏵ 1	2024-07-01 13:38:05	announced

Dataset with its publication pending

submitter keyword: fibrosis, ADAMTS12, extracellular matrix

Univ.-Prof. Dr. med. Rafael Kramann
contact affiliation	Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany.
contact email	rkramann@gmx.net
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
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/2024/07/PXD040152

PRIDE project URI

• PRIDE
  1. PXD040152
     1. Label: PRIDE project
     2. Name: ADAMTS12 serves as a checkpoint in fibrosis that controls migration and expansion of injury-responsive fibroblasts