Dataset Information

A proteomics resource for human iPSC-derived endothelial cells (iEC) - human FOXF2 KO versus WT control

ABSTRACT: FOXF2, a major risk gene for stroke and SVD, the mechanisms of which are insufficiently understood. CRISPR/Cas9-mediated knockout of FOXF2 induced key features of BBB dysfunction, including compromised cell junction integrity, decreased transendothelial electrical resistance and dysregulated caveolae formation. Proteomic analysis of human iPSC derived endothelial cells revealed an impairment of pathways related to endocytosis and cell junctions, confirming a role of FOXF2 in BBB function. The observed disease features phenocopy those seen in an endothelial cell-specific mouse model of Foxf2 deficiency that we have developed in parallel, validating the relevance of our human BBB model to investigate neurovascular disorders.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Pluripotent Stem Cell, Microvascular Endothelial Cell

DISEASE(S): Brain Small Vessel Disease

SUBMITTER: Stephan Mueller

LAB HEAD: Stefan F.

PROVIDER: PXD051960 | Pride | 2025-09-02

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	AGMD_2401_P1G10_Rep_01_Slot2-36_1_10775.d.zip	Other
	AGMD_2401_P1G10_Rep_02_Slot2-30_1_10769.d.zip	Other
	AGMD_2401_P1G10_Rep_03_Slot2-32_1_10771.d.zip	Other
	AGMD_2401_P1G10_Rep_04_Slot2-33_1_10772.d.zip	Other
	AGMD_2401_P1G10_Rep_05_Slot2-35_1_10774.d.zip	Other

Items per page:

1 - 5 of 11

Similar Datasets

Project description:Age-related decline in brain endothelial cell (BEC) function critically contributes to cerebrovascular and neurodegenerative disease. Comprehensive atlases of the BEC transcriptome have become available but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting (MACS)-based mouse BEC enrichment protocol compatible with high-resolution mass-spectrometry and analysed the profiles of protein abundance changes across multiple time points between 3 and 18 months of age and identified Arf6 as one of the most prominently downregulated vesicle-mediated transport protein during BEC aging. To understand the role of ARF6 in human ECs, first we compared GFP-AAV treated human iECs differentiated from ARF6-KO vs WT iPSCs, next we compared ARF6-GFP-AAV vs GFP-AAV treated iECs differentiated from WT iPSCs. During the ARF6-KO vs WT iEC comparison we found 983 vs 741 proteins significantly down- and upregulated, respectively. Enrichment analyses of significantly downregulated proteins revealed mRNA processing among the most significantly affected biological processes. During the ARF6-GFP-AAV vs GFP-AAV treated WT iEC comparison we found 1106 vs 1218 proteins significantly down- and upregulated, respectively. Enrichment analyses of significantly upregulated proteins revealed endocytic recycling, retrograde transport (endosome to Golgi), and ER-Golgi vesicle-mediated transport among the most significantly affected biological processes. Specifically, ARF6 and its binding-protein GGA2, DNM1L and several subunits of the Conserved oligomeric Golgi complex (COG) were upregulated. Our approach uncovered changes not picked up by transcriptomic studies such as accumulation of vesicle cargo and receptor ligands including Apoe, a major regulator of brain lipid metabolism. Proteomic analysis of BECs from Apoe deficient mice revealed a signature of accelerated aging. To explore the role of APOE in human endothelial cells, in this experiment we compared human iECs differentiated from APOE-KO and WT iPSCs and found 326 significantly altered proteins. Enrichment analyses of significantly downregulated proteins revealed vesicle-mediated transport and vesicle fusion to be among the most significantly affected biological processes. Specifically, among the 34 significantly altered vesicle-mediated transport proteins 26 were downregulated. Accordingly, we found reduced levels of endocytosis of FM1-43FX in newly formed vesicles in APOE-KO iECs.

Dataset Information

A proteomics resource for human iPSC-derived endothelial cells (iEC) - human FOXF2 KO versus WT control

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets