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Series GSE147693 Query DataSets for GSE147693
Status Public on Mar 30, 2020
Title Therapeutically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary With advances in single-cell genomics, molecular signatures of cells comprising the brain vasculature are revealed in unprecedented detail, yet the ageing-associated cell subtype transcriptomic changes which may contribute to neurovascular dysfunction in neurodegenerative diseases remain elusive. Here, we performed single-cell transcriptomic profiling of brain endothelial cells (EC) in young adult and aged mice to characterize their ageing-associated genome-wide expression changes. We identified zonation-dependent transcriptomic changes in aged brain EC subtypes, with capillary ECs exhibiting the most transcriptomic alterations. Pathway enrichment analysis revealed altered immune/cytokine signaling in ECs of all vascular segments, while functional changes impacting the blood-brain barrier (BBB) and glucose/energy metabolism were most prominently implicated in ECs of the capillary bed – the primary site where ECs and other neurovascular unit (NVU) cell types closely interact and coordinate to regulate BBB and cerebral blood flow in health and diseased conditions. Furthermore, an overrepresentation of Alzheimer’s disease (AD)-associated genes identified from GWAS studies was evident among the human orthologs of differentially expressed genes of aged capillary ECs but not other EC subtypes. Importantly, for numerous EC-enriched differentially expressed genes with important functional roles at the BBB and/or association with AD, we found concordant expression changes in human aged or AD brains. Finally, we demonstrated that treatment with exenatide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, strongly reverses transcriptomic changes in ECs and largely reduces BBB leakage in the aged brain. Thus, our study revealed novel vascular ageing-associations of AD in the brain capillary endothelium, and provides insights into detailed transcriptomic alterations underlying brain EC ageing that are complex with subtype specificity yet amenable to pharmacological interventions.
Overall design Perform single cell transcriptome sequencing of young, aged and drug treatment groups with each 3 replications.
Contributor(s) Ko H
Citation(s) 32887883
Submission date Mar 29, 2020
Last update date Sep 07, 2020
Contact name Ho Ko
Organization name The Chinese University of Hong Kong
Department Medicine and Therapeutics
Lab Ko Lab, Division of Neurology
Street address 30-32 Ngan Shing Street, Shatin
City Hong Kong
ZIP/Postal code 999077
Country China
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (9)
GSM4443373 Young1
GSM4443374 Young2
GSM4443375 Young4
BioProject PRJNA616112
SRA SRP254460

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Supplementary file Size Download File type/resource
GSE147693_barcodes.tsv.gz 283.0 Kb (ftp)(http) TSV
GSE147693_genes.tsv.gz 122.3 Kb (ftp)(http) TSV
GSE147693_matrix.mtx.gz 205.9 Mb (ftp)(http) MTX
GSE147693_meta.csv.gz 2.1 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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