PXD052254

PXD052254 is an original dataset announced via ProteomeXchange.

Title	RYR2-deficient human hiPSC-derived cardiomyocyte protein expression
Description	Creation of disease models utilizing hiPSCs in combination with CRISPR/Cas9 gene editing enable mechanistic insights into differential pharmacological responses. This allows translation of efficacy and safety findings from a healthy to a diseased state and provides a means to predict clinical outcome sooner during drug discovery. Calcium handling disturbances including reduced expression levels of the type 2 ryanodine receptor (RYR2) are linked to cardiac dysfunction; here we have created a RYR2 deficient human cardiomyocyte model that mimics some aspects of heart failure. RYR2 deficient cardiomyocytes show differential pharmacological responses to L-type channel calcium inhibitors. Phenotypic and proteomic characterization reveal novel molecular insights with altered expression of structural proteins including CSRP3, SLMAP, and metabolic changes including upregulation of the pentose phosphate pathway and increased sensitivity to redox alterations. This genetically engineered in vitro cardiovascular model of RYR2 deficiency supports the study of pharmacological responses in the context of calcium handling and metabolic dysfunction enabling translation of drug responses from healthy to perturbed cellular states.
HostingRepository	PRIDE
AnnounceDate	2024-06-20
AnnouncementXML	Submission_2024-06-20_03:16:38.142.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Piotr Grabowski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-14 04:22:42	ID requested
⏵ 1	2024-06-20 03:16:38	announced

10.3389/FCVM.2024.1357315;

submitter keyword: hiPSCs,human, RYR2, LC-MS/MS, cell line

Piotr Grabowski
contact affiliation	AstraZeneca
contact email	piotr.grabowski1@astrazeneca.com
lab head
Piotr Grabowski
contact affiliation	AstraZeneca
contact email	piotr.grabowski1@astrazeneca.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/2024/06/PXD052254

PRIDE project URI

• PRIDE
  1. PXD052254
     1. Label: PRIDE project
     2. Name: RYR2-deficient human hiPSC-derived cardiomyocyte protein expression