PXD049208

PXD049208 is an original dataset announced via ProteomeXchange.

Title	An iPSC-derived bio-inspired scaffold modelling the structure and the effects of extracellular matrix in cardiac fibrosis
Description	Cardiac fibrosis occurs following insults to the myocardium and is characterized by the abnormal accumulation of non-compliant extracellular matrix (ECM), which compromises cardiomyocyte (CMs) contractile activity and eventually leads to heart failure. This phenomenon is driven by the differentiation of cardiac fibroblasts (cFbs) into myofibroblasts and results in changes in ECM biochemical and structural properties. The lack of predictive in vitro models of heart fibrosis has so far hampered the search for innovative treatments. Here, we adopted a protocol to generate cFbs from human induced pluripotent stem cells (iPSCs) and activate them to a myofibroblast phenotype by tuning basic fibroblast growth factor (bFGF) and transforming growth factor beta 1 (TGF-β) signalling. We next confirmed that TGF-β stimulation prompted iPSC-derived cells to acquire key features of myofibroblasts, like SMAD2/3 nuclear shuttling, the formation of aligned alpha-smooth muscle actin (α-SMA)-rich stress fibres and increased focal adhesions (FAs) assembly. Additionally, we devised a single-step decellularization protocol to obtain and thoroughly characterize the biochemical and mechanical properties of the ECM secreted by activated cFbs. After revealing that iPSC-derived myofibroblasts secrete an abundant, collagen-rich and stiff ECM characterized by distinct viscoelastic properties, we demonstrated that this pro-fibrotic ECM activates mechanosensitive pathways in iPSC-derived CMs (iPSC-CMs), impacting their shape, sarcomere length, phenotype and calcium handling properties. We thus propose these human bio-inspired matrices as animal-free, isogenic CM culture substrates recapitulating key pathophysiological changes occurring at the cellular level during cardiac fibrosis.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_13:12:54.500.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Václav Pustka
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-06 07:05:12	ID requested
⏵ 1	2025-05-06 13:12:55	announced

10.1016/j.trsl.2024.07.003;

Niro F, Fernandes S, Cassani M, Apostolico M, Oliver-De La Cruz J, Pereira-Sousa D, Pagliari S, Vinarsky V, Zdr, á, hal Z, Potesil D, Pustka V, Pompilio G, Sommariva E, Rovina D, Maione AS, Bersanini L, Becker M, Rasponi M, Forte G, Fibrotic extracellular matrix impacts cardiomyocyte phenotype and function in an iPSC-derived isogenic model of cardiac fibrosis. Transl Res, 273():58-77(2024) [pubmed]

submitter keyword: disease modelling, decellularized extracellular matrix (dECM), cardiac fibrosis, iPSC-derived-cardiac fibroblasts (iPSC-cFbs),Induced pluripotent stem cells (iPSCs)

Zbynek Zdrahal
contact affiliation	Proteomics Core Facility and Research Group Proteomics, CEITEC-MU, Masaryk University, Brno, Czech Republic
contact email	zdrahal@sci.muni.cz
lab head
Václav Pustka
contact affiliation	Proteomics Core Facility and Research Group Proteomics CEITEC-MU Masaryk University Brno, Czech Republic
contact email	vaclav.pustka@ceitec.muni.cz
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/2025/05/PXD049208

PRIDE project URI

• PRIDE
  1. PXD049208
     1. Label: PRIDE project
     2. Name: An iPSC-derived bio-inspired scaffold modelling the structure and the effects of extracellular matrix in cardiac fibrosis