PXD055124-1

PXD055124 is an original dataset announced via ProteomeXchange.

Title	Endothelial Colony Forming Cells Characteristics in a healthy and VWD patient cohort.
Description	Background Endothelial cells are crucial for hemostasis as they produce Von Willebrand factor (VWF). Von Willebrand Disease (VWD) results from a deficiency or defects in VWF, However, diagnosis is difficult due to large differences between gene variants and bleeding phenotype. Here, we analyze the endothelial compartment of patients with VWD using Endothelial Colony Forming Cells (ECFCs). Methods 13 healthy controls and 10 patients were included and a total of 29 ECFC clones were derived. Plasma was analyzed and ECFC gene expression was measured by qPCR which was used to characterize clones. ECFCs were then morphologically and functionally tested by ELISA, imaging, scratch assay and mass spectrometry. Results VWF plasma levels and activity was reduced in patients, although values were higher than historically measured. Through hierarchical clustering of RNA expression profiles, we classified ECFCs into 2 clusters. Patients were matched with controls from the same cluster. Patient ECFCs did not show a uniform phenotype, but 3 of the 5 patients that did not respond to DDAVP showed clear retention of VWF in the endoplasmic reticulum. Furthermore, MS data showed proteomic clustering overlapping with RNA profiles and revealed a third group from lymphatic origin. An inverse protein correlation was seen between VWF levels and WPB count and cell area. No clear patient phenotype was observed but unique proteins were downregulated per clone. Conclusion This study investigates a broad panel of ECFCs derived from both healthy and diseased donors through comprehensive characterization using functional assays and proteomics. It emphasizes the current opportunities and challenges of utilizing ECFCs as a model to study WPB-specific mechanisms, while also providing an extensive overview of the molecular regulation of WPB machinery across endothelial cells and its functional implications.
HostingRepository	PRIDE
AnnounceDate	2024-11-28
AnnouncementXML	Submission_2024-11-28_07:28:45.957.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stijn Groten
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-23 04:08:15	ID requested
⏵ 1	2024-11-28 07:28:46	announced

Dataset with its publication pending

submitter keyword: proteomics, endothelial cell,ECFC, VWD

Maartje van den Biggelaar
contact affiliation	Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands
contact email	m.vandenbiggelaar@sanquin.nl
lab head
Stijn Groten
contact affiliation	Sanquin Research
contact email	s.groten@sanquin.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055124
     1. Label: PRIDE project
     2. Name: Endothelial Colony Forming Cells Characteristics in a healthy and VWD patient cohort.