Direct transcriptomic comparison of xenobiotic metabolism and toxicity pathway induction of airway epithelium models at an air-liquid interface generated from induced pluripotent stem cells and primary bronchial epithelial cells.
Direct transcriptomic comparison of xenobiotic metabolism and toxicity pathway induction of airway epithelium models at an air-liquid interface generated from induced pluripotent stem cells and primary bronchial epithelial cells.
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DOI：
10.1007/s10565-022-09726-0
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发表时间：
2023-02
影响因子：
6.1
通讯作者：
中科院分区：
文献类型：
--
作者：
气道上皮是吸入空气和呼吸道组织之间的主要屏障，因此是与进入人体的异生物质接触的重要点。最近的几项研究表明，在空气-液体界面（ALI）生长的气道的体外模型可以特别有用，以获得有关化学化合物的毒性的机制信息。然而，这样的方法不太适合高通量，因为原代细胞不能在培养物中无限扩增以获得可持续数量的细胞。近年来，诱导多能干细胞（iPSC）已成为模拟肺部气道的流行选择，但尽管该领域取得了进展，但迄今为止尚未评估此类模型代谢异生化合物的能力以及它们与原发性支气管气道模型（pBAE）的比较。在这里，我们通过TempoSeq（寡核苷酸定向测序）报告了iPSC衍生的气道模型（iBAE）与初级支气管气道模型（pBAE）的比较分析。iBAE和pBAE在ALI时进行分化，然后在5种化合物筛选中进行评估，并将每种化合物暴露于亚致死浓度24小时。我们发现，尽管异生物质代谢基因的表达较低，iBAE同样预测的毒性途径相比，pBAE模型。我们的研究结果表明，在ALI的iPSC气道模型显示吸入毒性评估的前景与进一步的发展。在线版本包含补充材料，可通过10.1007/s10565-022-09726-0获得。
The airway epithelium represents the main barrier between inhaled air and the tissues of the respiratory tract and is therefore an important point of contact with xenobiotic substances into the human body. Several studies have recently shown that in vitro models of the airway grown at an air–liquid interface (ALI) can be particularly useful to obtain mechanistic information about the toxicity of chemical compounds. However, such methods are not very amenable to high throughput since the primary cells cannot be expanded indefinitely in culture to obtain a sustainable number of cells. Induced pluripotent stem cells (iPSCs) have become a popular option in the recent years for modelling the airways of the lung, but despite progress in the field, such models have so far not been assessed for their ability to metabolise xenobiotic compounds and how they compare to the primary bronchial airway model (pBAE). Here, we report a comparative analysis by TempoSeq (oligo-directed sequencing) of an iPSC-derived airway model (iBAE) with a primary bronchial airway model (pBAE). The iBAE and pBAE were differentiated at an ALI and then evaluated in a 5-compound screen with exposure to a sub-lethal concentration of each compound for 24 h. We found that despite lower expression of xenobiotic metabolism genes, the iBAE similarly predicted the toxic pathways when compared to the pBAE model. Our results show that iPSC airway models at ALI show promise for inhalation toxicity assessments with further development. The online version contains supplementary material available at 10.1007/s10565-022-09726-0.
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DOI：
10.1002/stem.3422
发表时间：
2021-10
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Djidrovski I;Georgiou M;Hughes GL;Patterson EI;Casas-Sanchez A;Pennington SH;Biagini GA;Moya-Molina M;van den Bor J;Smit MJ;Chung G;Lako M;Armstrong L
通讯作者：
Armstrong L
影响因子：
3.7
作者：
Bushel PR;Paules RS;Auerbach SS
通讯作者：
Auerbach SS
DOI：
10.1165/ajrcmb.10.3.8117445
发表时间：
1994-03-01
影响因子：
6.4
作者：
DEJONG, PM;VANSTERKENBURG, MAJA;PONEC, M
通讯作者：
PONEC, M
影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D
影响因子：
3.7
作者：
House JS;Grimm FA;Jima DD;Zhou YH;Rusyn I;Wright FA
通讯作者：
Wright FA