Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A proteomics resource for human iPSC-derived endothelial cells (iEC), smooth muscle cells (iSMC), pericytes (iPC) and astrocytes (iAS) in comparison to iPSCs and human primary cells - technical replicates

ABSTRACT: Function and integrity of the blood-brain-barrier (BBB) is crucial for brain homeostasis, and its malfunction critically contributes to neurovascular and neurodegenerative disorders, including cerebral small vessel disease (SVD), a common cause of stroke and vascular dementia. So far, mechanistic studies on BBB function have been mostly conducted in mice and non-physiological in vitro models, which recapitulate disease features, but often lack complex phenotypes, have limited translatability to humans, and pose challenges for drug discovery. Therefore, we aimed to establish a fully iPSC-derived 3D model of the human blood-brain-barrier. To characterize and validate our somatic cell differentiation protocols we compared our iPSC-derived cells with commercially available human primary cells: brain microvascular endothelial cells (pEC), human umbilical vein endothelial cells (HUVEC), brain vascular pericytes (pPC), brain vascular smooth muscle cells (pSMC) and midbrain astrocytes (pAS).

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Pluripotent Stem Cell, Smooth Muscle Cell, Astrocyte, Pericyte Cell, Microvascular Endothelial Cell

SUBMITTER: Stephan Mueller

LAB HEAD: Stefan F.

PROVIDER: PXD051959 | Pride | 2025-09-08

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	HUVEC_1.zip	Other
	HUVEC_2.zip	Other
	HUVEC_3.zip	Other
	HUVEC_4.zip	Other
	HUVEC_5.zip	Other

Items per page:

1 - 5 of 51

Similar Datasets

A proteomics resource for human iPSC-derived endothelial cells (iEC), smooth muscle cells (iSMC), pericytes (iPC) and astrocytes (iAS) in comparison to human primary cells - technical and biological replicates

Project description:Integrity of the blood-brain barrier (BBB) is critical for brain homeostasis, and its malfunction contributes to neurovascular and neurodegenerative disorders. So far, mechanistic studies on BBB function have been mostly conducted in rodent and non-physiological in vitro models, which recapitulate some disease features, but have limited translatability to humans and pose challenges for drug discovery. Here we report on a fully human iPSC-derived, microfluidic 3D BBB model consisting of endothelial cells (EC), mural cells, and astrocytes. Our model expresses typical cell fate markers, forms a barrier in vessel-like tubes, and enables perfusion, including with human blood. We optimized iPSC differentiations and validated cellular fates by comparison to published datasets and extensive benchmarking vs. primary cells with proteomic profiles provided in an online database (https://dbNeuroVasP.isd-muc.de).

2025-09-08 | PXD066414 | Pride

Expression analysis in brain endothelial cells of Gαq/11beKO mice to elucidate CO2-induced vasoreactivity mechanism

Project description:CO2-induced vasoreactivity is an important mechanism to remove CO2 from the brain. Our previous work has shown that in brain endothelial cells Gαq and Gα11, that can replace each other and induce a common intracellular pathway, are required for normal vascular reactivity to CO2 stimulation. Additionally, we found different effects on vascular diameter dependent on the brain area. In the cortex, vessel dilate as response to CO2 stimulation, in the retrotrapezoid nucleus (RTN) of the brainstem, vessels constrict upon CO2 stimulation. To examine the potential basis for the opposing effects of CO2 on the vascular reactivity in brainstem compared to other brain areas, we prepared cortical and brainstem vessel fragments of control and Gαq/11beKO mice and performed microarrays to determine mRNA expression.

2019-12-20 | E-MTAB-8521 | biostudies-arrayexpress

Mass-spectrometry analysis of isolated brain vessels from vehicle treated Foxf2iECKO, vehicle-treated Ctrl, and AKB-9778 treated Foxf2iECKO mice

Project description:To further characterize the role of endothelial Foxf2 in the maintenance of vascular function and examine a possible mediating effect of Tie2 signaling, we pharmacologically modulated Tie2 activity in mice and performed subsequent in vivo analyses together with studies on isolated brain vessels. Specifically, we applied AKB-9778, a selective small molecule inhibitor of vascular endothelial protein tyrosine phosphatase (Ptprb, VE-PTP) previously shown to stabilize the vasculature through Tie2 activation (Saharinen, et al., 2016; Shen et al., 2014). Mass-spectrometry analysis of isolated brain vessels from vehicle-treated Foxf2iECKO and Ctrl mice (Foxf2iECKO-Veh and Ctrl-Veh, respectively) confirmed the dysregulation of multiple proteins related to Tie2 signaling. Treatment with AKB-9778 for 48h restored their levels. Specifically, the abundance of Nos3, Nostrin and Gucy1b1 (implicated in nitric oxide metabolic process), Cldn5, Ctnnd1, Pecam1, and Rap1b (implicated in establishment of endothelial barrier), and Tie2, Flt1, and Itgb1 (implicated in angiogenesis) were all upregulated upon Tie2 activation. Collectively, these findings demonstrate that AKB-9778 rescues the deficiency of Tie2 signaling in mouse BECs lacking Foxf2.

2025-09-02 | PXD051839 | Pride

Transcriptome analysis of 3D model of blood-brain barrier exposed to West Nile virus (WNV)

Project description:Using RNA sequencing to map differentially expressed genes in the 3D model of the blood-brain barrier ( composed of human brain endothelial cells, human astrocytes, and human pericytes) challenged with WNV.

2021-01-01 | E-MTAB-9754 | biostudies-arrayexpress

Transcriptome analysis of 3D model of blood-brain barrier exposed to tick-borne encephalitis virus (TBEV)

2021-01-01 | E-MTAB-9755 | biostudies-arrayexpress

Mass-spectrometry analysis of vehicle or AKB-9778 treated FOXF2KO and WT human endothelial cells

Project description:To validate our results on Foxf2 related Tie2 signaling and explore their transferability to human cells, we studied human iPSC-derived endothelial cells (iECs). FOXF2KO and WT iECs (González-Gallego et al., in preparation) were treated with AKB-9778 or vehicle and assessed by proteomics. Similar to our results in mouse BECs, proteomic analysis revealed a dysregulation of multiple members of the TIE2 signaling pathway in vehicle treated FOXF2KO compared to WT iECs including TIE2 and NOS3. Moreover, treatment with AKB-9778 restored the levels of multiple TIE2 signaling related proteins. Collectively, these findings demonstrate that AKB-9778 rescues the deficiency of TIE2 signaling in human endothelial cells lacking FOXF2. González-Gallego, J. et al. A fully iPSC-derived 3D model of the human blood-brain-barrier for exploring neurovascular disease mechanisms and therapeutic interventions - in preparation, available from editorial office upon request.

2025-09-02 | PXD051855 | Pride

Transcriptome analysis of 3D model of blood-brain barrier exposed to Borrelia garini

2021-01-01 | E-MTAB-9753 | biostudies-arrayexpress

Immune cell infiltration into brain tumor microenvironment is mediated by Rab27-regulated vascular wall integrity

Project description:Aggressive brain tumors often exhibit immunologically ‘cold’ microenvironment, where the vascular barrier impedes effective immunotherapy in poorly understood ways. Tumor vasculature also plays a pivotal role in immunoregulation and antitumor immunity. Here we show that small GTPase Rab27 controls the vascular morphogenesis and permeability for blood content and immune effectors. Thus, in Rab27a/b double knock out (Rab27-dKO) mice, the brain vasculature is abnormally scarce while the blood vessels become dysmorphic and hyperpermeable in the context of brain tumors, including syngeneic glioblastoma. These defects are reflected in rearrangements of endothelial cell subpopulations with underlying diminution of venous endothelial subtype along with changes in gene and protein expression. Notably, Rab27-dKO brain endothelial cells exhibit deficient tight junctions, whereby they enable large-scale extravasation of cytotoxic T cells into the tumor mass. We show that Rab27-regulated vascular T cell infiltration can be exploited to enhance adoptive T cell therapy in syngeneic brain tumors.

2025-06-02 | PXD062939 | Pride

Single Cell Immuno-laser Microdissection Coupled to Label-free Proteomics to Reveal the Proteotypes of Human Brain Cells After Ischemia

Project description:Cerebral ischemia entails rapid tissue damage in the affected brain area causing devastating neurological disorders. The use of biomarkers in stroke might have a major impact in patients’ management, both in the diagnosis and the prognosis. Thus, the analysis of the brain proteome is a straightforward approach for the identification of specific biomarkers and for the detection of potential new therapeutic targets for neuroprotection or recovery strategies. In this study, post-mortem brain slices from ischemic stroke patients were obtained corresponding to infarcted (IC) and contralateral (CL) areas. By means of laser microdissection, neurons and blood brain barrier structures (BBB) were isolated and analyzed in a label-free manner on a LTQ Orbitrap Velos Pro MS following a gas phase fractionation approach for precursor ion selection. Ninety one proteins were identified only in neurons, 261 proteins only in BBB and 260 proteins in both cell types (peptides≥2). Gene ontology analyses revealed the alteration of metabolic processes after brain ischemia and also changes regarding catalytic activity and binding. Antioxidant activity and enzyme regulator activity appeared as cell-specific altered molecular functions. A total of 25 proteins showing p<0.05 and fold-change>|2| between IC and CL areas were considered significant in this study: 11 in neurons, 11 in BBB and 3 in both cell types. Twelve of these proteins were selected as candidates and analyzed by immunohistochemistry in independent brains. The MS findings were verified for neuronal SAHH2 and SRSF1 and for EAA2 in both cell types. In addition, SAHH2 showed its potential as prognostic biomarker when analyzed early in plasma of ischemic stroke patients. Therefore, our results will contribute to increase the knowledge about the molecular mechanisms of ischemic stroke pathology and launch new proteins that might represent putative biomarkers of brain ischemia or therapeutic targets.

2017-12-04 | PXD003519 | Pride

ApoE4 disrupts intracellular trafficking and iron homeostasis in an improved iPSC-based model of human brain endothelial cells

Project description:We compare the proteome of the brain endothelial cells obtained with the newly optimized protocol (iCE-BECs) to the primary human brain microvascular endothelial cells (HBMVECs) and the widely used immortalized brain endothelial cell line HCMECD3. The goal is to investigate the applicability of iCE-BECs for transport assays, measuring the expression of transporters and receptors with whole cell proteomics.

2025-08-08 | PXD062808 | Pride