Transcriptional and functional characterization of human intestinal organoid and monolayer models for IBD-therapeutic development

Intestinal organoids have the potential to replicate cellular diversity and functional biology of the human gut, suggesting their application in Inflammatory Bowel Disease (IBD) research. Insufficient characterization at the molecular, cellular, and functional level has remained a barrier to their use in drug discovery. We profile intestinal organoids and Transwell-monolayers derived from ileum and colon tissue of control and IBD subjects. Organoids and monolayers respond to optimized differentiation media with consistent expression and maturation patterns, including signatures of epithelial cell types found in the human gut. Both ileum- and colon-derived monolayers show acute sensitivity to cytokines with applicability for modeling epithelial barrier damage. Overall design: Instestinal organoid and monolayer cultures derived from healthy and IBD colon and ileum where grown in three different differentiation media

肠道类器官（Intestinal organoids）具备复现人类肠道细胞多样性与功能生物学特性的潜力，使其有望应用于炎症性肠病（Inflammatory Bowel Disease, IBD）相关研究。然而，其在分子、细胞及功能层面的表征不足，仍是制约其应用于药物研发的核心瓶颈。本研究对源自对照受试者与IBD患者回肠、结肠组织的肠道类器官及Transwell单层培养物（Transwell-monolayers）开展了全面表征分析。类器官与单层培养物可响应优化后的分化培养基，呈现出一致的基因表达与成熟模式，涵盖人类肠道上皮细胞各类群的特征谱。回肠与结肠来源的单层培养物均对细胞因子表现出显著敏感性，可用于构建上皮屏障损伤模型。研究整体设计：从健康个体与IBD患者的结肠、回肠组织中获取的肠道类器官及单层培养物，分别在三种不同的分化培养基中进行培养。