Background & Aims

Recent evidence has suggested that the intact intestinal epithelial barrier protects our body from a range of immune-mediated diseases. The epithelial layer has an impressive ability to reconstitute and repair upon damage and this process of repair increasingly is seen as a therapeutic target. In vitro models to study this process in primary intestinal cells are lacking.

Methods

We established and characterized an in vitro model of intestinal damage and repair by applying γ-radiation on small-intestinal organoids. We then used this model to identify novel regulators of intestinal regeneration.

Results

We identified hepatocyte nuclear factor 4α (HNF4α) as a pivotal upstream regulator of the intestinal regenerative response. Organoids lacking Hnf4a were not able to propagate in vitro. Importantly, intestinal Hnf4a knock-out mice showed impaired regeneration after whole-body irradiation, confirming intestinal organoids as a valuable alternative to in vivo studies.

Conclusions

In conclusion, we established and validated an in vitro damage–repair model and identified HNF4α as a crucial regulator of intestinal regeneration. Transcript profiling: GSE141515 and GSE141518.

中文翻译：

---

一种新型的损伤修复修复器官模型将HNF4α鉴定为肠道上皮再生的关键调节剂。

背景与目标

最近的证据表明，完整的肠上皮屏障可保护我们的身体免受一系列免疫介导的疾病的侵害。上皮层具有在损伤时重建和修复的令人印象深刻的能力，并且这种修复过程越来越被视为治疗目标。缺乏在原代肠细胞中研究该过程的体外模型。

方法

我们通过在小肠类器官上应用γ射线建立并表征了肠道损伤和修复的体外模型。然后，我们使用该模型来确定新型的肠道再生调节剂。

结果

我们确定了肝细胞核因子4α（HNF4α）作为肠再生反应的关键上游调节剂。缺少Hnf4a的类器官不能在体外繁殖。重要的是，肠道Hnf4a敲除小鼠在全身照射后显示出受损的再生能力，从而证实了肠道类器官是体内研究的一种有价值的替代方法。

结论

总之，我们建立并验证了体外损伤修复模型，并将HNF4α确定为肠道再生的关键调节剂。成绩单分析：GSE141515和GSE141518。