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ABSTRACT: Modeling the Blood-Brain Barrier Formation and Cerebral Cavernous Malformations in human PSCs- and primary tissue-derived organoids

PROVIDER: PRJNA1099409 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28642931.fastq.gz	Fastqsanger.gz
	SRR28642932.fastq.gz	Fastqsanger.gz
	SRR28642933.fastq.gz	Fastqsanger.gz
	SRR28642934.fastq.gz	Fastqsanger.gz
	SRR28642935.fastq.gz	Fastqsanger.gz

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Modeling the Blood-Brain Barrier Formation and Cerebral Cavernous Malformations in human PSCs- and primary tissue-derived organoids

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Project description:The human blood-brain barrier (hBBB) is a highly specialized structure that regulates passage across blood and CNS compartments. Despite its critical physiological role, there are no reliable in vitro models that can mimic hBBB development and function. Here, we constructed hBBB assembloids from brain and blood vessel organoids derived from human pluripotent stem cells. We validated the acquisition of BBB-specific molecular, cellular, transcriptomic, and functional characteristics and uncovered an extensive neuro-vascular crosstalk with a spatial pattern within hBBB assembloids. When we used patient-derived hBBB assembloids to model cerebral cavernous malformations (CCMs), we found that these assembloids recapitulated the cavernoma anatomy and BBB breakdown observed in patients. Upon comparison of phenotypes and transcriptome between patient-derived hBBB assembloids and primary human cavernomas tissues, we uncovered CCM-related molecular and cellular alterations. Taken together, we report hBBB assembloids that mimic core properties of the human BBB and identify a potentially underlying cause of CCMs.

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