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| Status |
Public on Jan 16, 2024 |
| Title |
Rescue of Impaired Blood-Brain Barrier in a Tuberous Sclerosis Complex Patient Derived Neurovascular Unit |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Tuberous sclerosis complex (TSC) is a multi-system genetic disease that causes benign tumors in the brain and other vital organs. The most debilitating symptoms result from involvement of the central nervous system and lead to a multitude of severe symptoms including seizures, intellectual disability, autism, and behavioral problems. TSC is caused by heterozygous mutations of either theTSC1orTSC2gene. Dysregulation of mTOR kinase with its multifaceted downstream signaling alterations is central to disease pathogenesis. Although the neurological sequelae of the disease are well established, little is known about how these mutations might affect cellular components and the function of the blood-brain barrier (BBB). We generated disease-specific cell models of the BBB by leveraging human induced pluripotent stem cell and microfluidic cell culture technologies. Using these microphysiological systems, we demonstrate that the BBB generated fromTSC2heterozygous mutant cells shows increased permeability which can be rescued with treatment with rapamycin, an mTOR kinase inhibitor, but also by wild type astrocytes.
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| Overall design |
To investigate how TSC mutations affect cellular components and functions of the BBB, pluripotent stem cells from healthy human tissue and from patients with heterozygous TSC mutations were grown using microfluidic cell culture with continual perfusion.
Gene expression profiling via bulk RNA-seq was performed on control and TSC-mutant cells.
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| Contributor(s) |
Brown JA, Faley SL, Judge M, Ward P, Ihrie RA, Carson R, Armstrong L, Sahin M, Wikswo JP, Ess KC, Neely DM |
| Citation(s) |
38168450, 38783199 |
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| Submission date |
Jun 26, 2023 |
| Last update date |
Jun 06, 2024 |
| Contact name |
Matthew Cottam |
| Organization name |
Vanderbilt University
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| Lab |
Creative Data Solutions
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| Street address |
2213 Garland Avenue South 9465
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| City |
Nashville |
| State/province |
TN |
| ZIP/Postal code |
37232 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA987721 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE235862_raw_counts.txt.gz |
552.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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