02403nas a2200433   4500000000100000008004100001260001500042653001600057653003700073653003200110653003000142653003100172653003200203653003200235653002800267100001200295700001300307700001000320700001600330700002500346700001200371700001300383700002500396700001900421700001200440700001500452700001700467700001700484700001600501700001500517700002200532700001600554700001900570700001500589245011100604856007200715520116800787022001401955       2024                            d  c2024-05-1510aAssembloids10acerebral cavernous malformations10ahuman PSC-derived organoids10ahuman blood-brain barrier10aneuro-vascular development10aneuro-vascular interactions10asingle-cell transcriptomics10aspatial transcriptomics1 aLan Dao1 aZhen You1 aLu Lu1 aTianyang Xu1 aAvijite Kumer Sarkar1 aHui Zhu1 aMiao Liu1 aRiccardo Calandrelli1 aGeorge Yoshida1 aPei Lin1 aYifei Miao1 aSarah Mierke1 aSrijan Kalva1 aHaining Zhu1 aMingxia Gu1 aSudhakar Vadivelu1 aSheng Zhong1 aL. Frank Huang1 aZiyuan Guo00aModeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids  uhttps://www.sciencedirect.com/science/article/pii/S19345909240014623 aThe 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.  a1934-5909