PXD016068

PXD016068 is an original dataset announced via ProteomeXchange.

Title	Swarms of specialized fibroblasts drive scarring through N-cadherin
Description	Injury in mammals induces a connective tissue response to either regenerate as before, or to scar. The fibroblastic actions and mechanisms that underlie these connective tissue responses remain obscure, as direct observation in animals is too difficult and current assays do not faithfully reproduce physiology. Here, we developed a skin explant technique termed scar-in-a-dish (SCAD) that faithfully recapitulates uniform scars with contraction and reveals how scarring occurs in unprecedented detail. By growing mouse SCADs, with a traceable scar-progenitor fibroblast lineage, we observed previously unseen intercellular connections form between scar-progenitors that then collectively swarm into the nascent wound in highly regular periodic movements that progressively contract the skin and form scars. Swarming is exclusive to scar progenitors and absent from oral cavity fibroblasts that regenerate scarless. By testing a panel of adhesion molecules that might instigate intercellular connections, we found swarming was induced by the upregulation of N-cadherin in scar progenitors. Impeding N-cadherin binding inhibited swarming and contraction, and led to reduced scarring in SCAD and in mice. Blocking N-cadherin and scar-progenitor swarming thus provides a novel therapeutic space to curtail pathological fibrotic responses across a range of medical settings.
HostingRepository	PRIDE
AnnounceDate	2020-10-26
AnnouncementXML	Submission_2020-12-04_01:01:44.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christoph Mayr
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-29 08:02:28	ID requested
1	2020-10-26 00:05:48	announced
⏵ 2	2020-12-04 01:01:45	announced	2020-12-04: Updated publication reference for PubMed record(s): 33159076.

Jiang D, Christ S, Correa-Gallegos D, Ramesh P, Kalgudde Gopal S, Wannemacher J, Mayr CH, Lupperger V, Yu Q, Ye H, M, ü, ck-H, ä, usl M, Rajendran V, Wan L, Liu J, Mirastschijski U, Volz T, Marr C, Schiller HB, Rinkevich Y, Injury triggers fascia fibroblast collective cell migration to drive scar formation through N-cadherin. Nat Commun, 11(1):5653(2020) [pubmed]

curator keyword: Biological

submitter keyword: Scar progenitors, scarring, contraction, SCAD, cell lineage, live imaging, collective migration, fibroblastic swarm, N-cadherin

Yuval Rinkevich
contact affiliation	Helmholtz Zentrum München, Institute of Lung Biology and Disease, Group Regenerative Biology and Medicine, Munich, Germany, Member of the German Centre for Lung Research (DZL)
contact email	yuval.rinkevich@helmholtz-muenchen.de
lab head
Christoph Mayr
contact affiliation	CPC/ILBD HemholtzZentrum München
contact email	Christoph.Mayr@helmholtz-muenchen.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/2020/10/PXD016068

PRIDE project URI

• PRIDE
  1. PXD016068
     1. Label: PRIDE project
     2. Name: Swarms of specialized fibroblasts drive scarring through N-cadherin