诱导多能干细胞
囊性纤维化
细胞生物学
囊性纤维化跨膜传导调节器
干细胞
生物
细胞分化
定向微分
胚胎干细胞
遗传学
基因
作者
Amy P. Wong,Christine E. Bear,Stephanie Chin,Peter Pasceri,Tadeo Thompson,Ling-Jun Huan,Félix Ratjen,James Ellis,Janet Rossant
摘要
Wong et al. differentiate human pluripotent stem cells into mature airway epithelial cells expressing CFTR, a gene involved in cystic fibrosis. Applying the method to induced pluripotent stem cells derived from cystic fibrosis patients provides a renewable source of cells for drug screening. Cystic fibrosis (CF) is a fatal genetic disease caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, which regulates chloride and water transport across all epithelia and affects multiple organs, including the lungs. Here we report an in vitro directed differentiation protocol for generating functional CFTR-expressing airway epithelia from human embryonic stem cells. Carefully timed treatment by exogenous growth factors that mimic endoderm developmental pathways in vivo followed by air-liquid interface culture results in maturation of patches of tight junction–coupled differentiated airway epithelial cells that demonstrate active CFTR transport function. As a proof of concept, treatment of CF patient induced pluripotent stem cell–derived epithelial cells with a small-molecule compound to correct for the common CF processing mutation resulted in enhanced plasma membrane localization of mature CFTR protein. Our study provides a method for generating patient-specific airway epithelial cells for disease modeling and in vitro drug testing.
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