PXD041780

PXD041780 is an original dataset announced via ProteomeXchange.

Title	Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity
Description	The microvasculature plays a key role in tissue perfusion, transport of mediators, and exchange of gases and metabolites to and from tissues. Microvascular dysfunction has emerged as an important contributor to cardiovascular diseases. In this study we used human blood vessel organoids (BVOs) as a model of the microvasculature to delineate the mechanisms of microvascular dysfunction caused by metabolic rewiring. BVOs fully recapitulated key features of the normal human microvasculature, including reliance of mature endothelial cells (ECs) on glycolytic metabolism, as concluded from metabolic flux assays using 13C-glucose labelling and mass spectrometry-based metabolomics. Pharmacological targeting of PFKFB3, a potent activator of glycolysis, with two different chemical inhibitors resulted in rapid BVO restructuring, vessel regression with reduced pericyte coverage. PFKFB3 mutant BVOs also displayed similar structural remodelling compared to control BVOs. Proteomic analysis of the BVO secretome revealed remodelling of the extracellular matrix and differential expression of paracrine mediators such as CTGF. Treatment with recombinant CTGF recovered tight junction formation and increased pericyte coverage in microvessels. Our metabolic and proteomics findings demonstrate that BVOs rapidly undergo restructuring in response to metabolic changes and identify CTGF as a critical paracrine regulator of microvascular integrity.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:44:25.085.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD041780
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Xiaoke Yin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-24 09:02:18	ID requested
1	2023-09-13 04:36:46	announced
⏵ 2	2023-11-14 08:44:25	announced	2023-11-14: Updated project metadata.

10.6019/PXD041780;

submitter keyword: Cardiovascular Diseases, Blood Vessel Organoids, Metabolic rewiring, Induced Pluripotent Stem Cells,Microvascular dysfunction, Glycolysis

Manuel Mayr
contact affiliation	School of Cardiovascular & Metabolic Medicine and Sciences, King's College London, London, United Kingdom
contact email	manuel.mayr@kcl.ac.uk
lab head
Xiaoke Yin
contact affiliation	Cardiovascular Division, King's College London
contact email	xiaoke.yin@kcl.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041780
     1. Label: PRIDE project
     2. Name: Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity