来自患者的结肠从未患病的组织中获得的结肠保留了炎症性肠道疾病特异性的转录基因特征
Tatiana A Karakasheva1, Yusen Zhou1,2, Hongbo M Xie2
1Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
人类的肠状体和结肠状体准确地反映了克罗恩病中的转录差异. 这证实了它们在研究炎症性肠病和从未受到影响的组织中识别疾病状态时的有效性.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 翻译医学是一种翻译医学.
背景情况:
- 炎症性肠病 (IBD) 的特点是粘膜损伤和上皮屏障破坏.
- 人体肠状体和结肠状体是研究IBD上皮层方面至关重要的床上模型.
- 这项研究旨在确定这些模型中健康和IBD受试者之间的持续转录差异,即使使用疾病分离的组织.
研究的目的:
- 与健康对照人群相比,定义和确认患者衍生的肠道和结肠道的转录差异.
- 评估这些转录签名是否在体外保持.
- 评估这些模型在诊断IBD和识别疾病特征方面的潜力.
主要方法:
- 在活检和匹配儿童克罗恩病患者和对照者的肠状/结肠状培养物上进行了RNA测序.
- 生物信息学和机器学习分析被用于识别差异性基因表达模式.
- 用细胞因子治疗晚期通过的体,以评估转录变化的持久性.
主要成果:
- 在克罗恩病活检和相应的肠道/肠道之间的上调途径中观察到显著的重叠.
- 关键上调的KEGG通路包括细胞因子-细胞因子受体相互作用,化学因子信号传递和Toll-like受体信号传递.
- 机器学习模型准确地预测了活检位置和供体疾病状况,而叶肠状体数据预测了直肠结肠体中的克罗恩病.
结论:
- 克罗恩病活检的转录档案可靠地重复在患者衍生的肠道和结肠道中.
- 来自疾病分离组织的转录组数据可以识别克罗恩病患者,突出显示模型的翻译潜力.
- 患者衍生出的肠和结肠被认可为IBD研究和药物开发的关键工具.
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