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Title: A Human Model of Cerebral Amyloid Angiopathy Using Neural Crest-Derived Vascular Smooth Muscle Cells      
dateReleased:
01-21-2015
description:
There is a growing recognition of cerebrovascular contribution to neurodegenerative diseases. Cerebral amyloid angiopathy (CAA), characterised by amyloid-beta (Aβ) deposits in the walls of intracerebral and leptomeningeal arteries, is evident in a majority of Alzheimer’s disease patients and aged people. Here, we leverage on human pluripotent stem cells to generate vascular smooth muscle cells (SMCs) from neural crest progenitors, recapitulating brain vasculature-specific attributes in Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural crest-derived SMCs to mediate Aβ uptake and intracellular proteasomal degradation. Hypoxia significantly compromises the ability of SMCs in Aβ clearance by suppressing LRP1 expression. This enables us to develop an assay of Aβ uptake using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high throughput format, demonstrating the value of stem cell-based phenotypic screening for novel CAA therapeutics and drug repurposing. We adopted our previous SMC differentiation protocol (Cheung et al., 2012) to differentiate this intermediate neural crest population using platelet-derived growth factor BB (PDGF-BB, 10 ng/ml) and transforming growth factor-beta 1 (TGF-β1, 2ng/ml) for another 12 days. The resultant neural crest-derived SMCs (NCSMC) were then characterised in comparison to neuroectoderm-derived SMCs (NESMC) (Cheung et al., 2012) and positive control, human brain vascular SMCs (BVSMC).
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-55173
refinement:
raw
alternateIdentifiers:
55173
keywords:
functional genomics
dateModified:
01-27-2015
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-10904
name:
Illumina HumanHT-12 V4.0 expression beadchip (gene symbol)
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-55173/E-GEOD-55173.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-55173/E-GEOD-55173.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55173
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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