类有机物
细胞生物学
胚胎干细胞
人脑
生物
神经科学
基因
遗传学
作者
Barış Çakır,Yangfei Xiang,Yoshiaki Tanaka,Mehmet H. Kural,Maxime Parent,Young-Jin Kang,Kayley Chapeton,Benjamin Patterson,Yifan Yuan,Chuan He,Micha Sam Brickman Raredon,Jake Dengelegi,Kun-Yong Kim,Pingnan Sun,Ming Zhong,Sang-Ho Lee,Prabir Patra,Fahmeed Hyder,Laura E. Niklason,Sang‐Hun Lee,Young-sup Yoon,In‐Hyun Park
出处
期刊:Nature Methods
[Springer Nature]
日期:2019-10-07
卷期号:16 (11): 1169-1175
被引量:559
标识
DOI:10.1038/s41592-019-0586-5
摘要
Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide a platform to study human brain development and diseases in complex three-dimensional tissue. However, current hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to the inner-most parts of hCOs. We engineered hESCs to ectopically express human ETS variant 2 (ETV2). ETV2-expressing cells in hCOs contributed to forming a complex vascular-like network in hCOs. Importantly, the presence of vasculature-like structures resulted in enhanced functional maturation of organoids. We found that vascularized hCOs (vhCOs) acquired several blood-brain barrier characteristics, including an increase in the expression of tight junctions, nutrient transporters and trans-endothelial electrical resistance. Finally, ETV2-induced endothelium supported the formation of perfused blood vessels in vivo. These vhCOs form vasculature-like structures that resemble the vasculature in early prenatal brain, and they present a robust model to study brain disease in vitro.
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