PXD040152 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-02-16 07:58:52 | ID requested | |
⏵ 1 | 2024-07-01 13:38:05 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: fibrosis, ADAMTS12, extracellular matrix |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD040152
- Label: PRIDE project
- Name: ADAMTS12 serves as a checkpoint in fibrosis that controls migration and expansion of injury-responsive fibroblasts