在分化过程中暴露于内分泌干扰化学物质会改变干细胞岛屿中的增殖成熟平衡
June H Gudmestad1, Lucas Unger1, Joao A Paulo2
1Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.
概括
内分泌干扰化学物质 (EDCs) 可以损害人类胰腺小岛的发育. 干细胞小岛 (SC小岛) 显示EDCs延迟小岛细胞成熟,为毒性测试提供了一个新的模型.
科学领域:
- 内分泌学 在内分泌学.
- 发育毒理学 发展毒理学
- 干细胞生物学 干细胞生物学
背景情况:
- 内分泌干扰化学物质 (EDC) 通过胰腺β细胞功能障碍与糖尿病有关.
- 对EDCs的发育暴露存在风险,但适合人类小岛发展的模型很少.
研究的目的:
- 评估从人类诱导多能干细胞 (iPSCs) 衍生出来的干细胞小岛 (SC-islets) 的实用性,作为EDC发育毒性的模型.
- 研究EDC混合物对人类小岛区分和发育的影响.
主要方法:
- 从人类iPSCs生成的SC岛屿.
- 暴露于差异化SC岛屿的双A,双S和跨-诺纳的混合物.
- 分析了转录特征和细胞增殖标记 (KI67).
主要成果:
- 暴露于EDC改变了SC岛屿的转录特征.
- 观察到β细胞成熟度标志物减少和增多的增殖标志物 (KI67).
- SC小岛的发展显示出早期阶段的特征,表明分化延迟.
结论:
- SC岛区分是评估EDC发育毒性的相关体外模型.
- 该模型的结果与体内研究一致,支持其用于化学安全评估.
- 这种模型有助于对内分泌发育障碍的机制研究.
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