A "living biobank" of Crohn's Disease

Patient-derived organoids (PDOs) from the colons of patients with Crohn's Disease (or healthy controls) were subjected to in-depth genotype, transcriptome and phenotype assessment. These studies revealed that CD may be classified broadly into two molecular subtypes, each with its unique profile of dysregulated celluar processes. We further show that these phenotypes can be rectified with matched therapeutics, hence making such intervention personalized. Findings show that CD-PDOs could serve as pre-clinical platforms for drug discovery and personalized medicine. Overall design: Patients representing various subtypes of Crohn's disease (CD) [Montreal classification-B1/2/3, perianal] were enrolled into this study to obtain tissue biopsies which would serve as source of adult stem cells for the generation of patient-derived organoids (PDOs). Standard cell biological, biochemical, functional and phenotypic assays were used to assess the PDOs for: 1) barrier integrity, 2) apoptosis, 3) proliferation, 4) ROS induced DNA/RNA damage; 5) senescence and DNA damage; 6) bacterial clearance, 7) induction of inflammatory cytokines, and morphology/growth characteristics. Please note that the cell biological, biochemical, and functional assays are not done on these GEO samples prior to RNA analysis, but characterization that is independent of the samples sequenced. The current records are the content of the associated manuscript to validate RNA seq findings.

克罗恩病（Crohn's Disease, CD）患者及健康对照者结肠来源的患者来源类器官（Patient-derived organoids, PDOs）接受了深度基因型、转录组及表型分析。本研究显示，CD可大致分为两种分子亚型，各自具备独特的细胞过程失调特征谱。本研究进一步证实，上述表型可通过匹配的治疗手段进行矫正，从而实现个体化干预。研究结果表明，克罗恩病来源的PDOs可作为药物研发与个体化医学的临床前研究平台。

研究整体设计如下：本研究纳入了符合各类克罗恩病亚型（依据蒙特利尔分型（Montreal classification）B1/2/3型及肛周型）的患者，获取其组织活检样本以作为成体干细胞来源，用于构建患者来源类器官（PDOs）。采用标准细胞生物学、生物化学、功能学及表型检测实验对PDOs进行以下指标检测：1）屏障完整性；2）细胞凋亡；3）细胞增殖；4）活性氧（Reactive Oxygen Species, ROS）诱导的DNA/RNA损伤；5）细胞衰老与DNA损伤；6）细菌清除能力；7）炎性细胞因子诱导水平，以及形态与生长特征。

请注意，本研究未针对本次RNA测序（RNA-seq）前的基因表达综合数据库（Gene Expression Omnibus, GEO）样本开展上述细胞生物学、生物化学及功能学实验，相关表征分析独立于已测序样本完成。本数据集当前的记录内容，旨在佐证相关手稿中所报道的RNA测序（RNA-seq）结果。