TY - JOUR
KW - Assembloids
KW - cerebral cavernous malformations
KW - human PSC-derived organoids
KW - human blood-brain barrier
KW - neuro-vascular development
KW - neuro-vascular interactions
KW - single-cell transcriptomics
KW - spatial transcriptomics
AU - Lan Dao
AU - Zhen You
AU - Lu Lu
AU - Tianyang Xu
AU - Avijite Kumer Sarkar
AU - Hui Zhu
AU - Miao Liu
AU - Riccardo Calandrelli
AU - George Yoshida
AU - Pei Lin
AU - Yifei Miao
AU - Sarah Mierke
AU - Srijan Kalva
AU - Haining Zhu
AU - Mingxia Gu
AU - Sudhakar Vadivelu
AU - Sheng Zhong
AU - L. Frank Huang
AU - Ziyuan Guo
AB - The human blood-brain barrier (hBBB) is a highly specialized structure that regulates passage across blood and central nervous system (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 blood-brain barrier (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 cavernoma tissues, we uncovered CCM-related molecular and cellular alterations. Taken together, we report hBBB assembloids that mimic the core properties of the hBBB and identify a potentially underlying cause of CCMs.
BT - Cell Stem Cell
DA - 2024-05-15
DO - 10.1016/j.stem.2024.04.019
N2 - The human blood-brain barrier (hBBB) is a highly specialized structure that regulates passage across blood and central nervous system (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 blood-brain barrier (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 cavernoma tissues, we uncovered CCM-related molecular and cellular alterations. Taken together, we report hBBB assembloids that mimic the core properties of the hBBB and identify a potentially underlying cause of CCMs.
PY - 2024
T2 - Cell Stem Cell
TI - Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids
UR - https://www.sciencedirect.com/science/article/pii/S1934590924001462
Y2 - 2024-05-24
SN - 1934-5909
ER -