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Rescue of Impaired Blood-Brain Barrier in a Tuberous Sclerosis Complex Patient Derived Neurovascular Unit

ABSTRACT: Rescue of Impaired Blood-Brain Barrier in a Tuberous Sclerosis Complex Patient Derived Neurovascular Unit

PROVIDER: PRJNA987721 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25031762_1.fastq.gz	Fastqsanger.gz
	SRR25031762_2.fastq.gz	Fastqsanger.gz
	SRR25031763_1.fastq.gz	Fastqsanger.gz
	SRR25031763_2.fastq.gz	Fastqsanger.gz
	SRR25031764_1.fastq.gz	Fastqsanger.gz

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Rescue of Impaired Blood-Brain Barrier in a Tuberous Sclerosis Complex Patient Derived Neurovascular Unit

Project description: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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