外侧出芽的肠道器官小体是一种相对简单的方法，可用于获取到顶层细胞表面，并在过去几年中引起了越来越多的科学兴趣。因此，可以使用外侧出芽的器官小体来进行疾病建模，以比较对底层与顶层细胞表面的不同效应。然而，这些“内外翻”的器官小体会相对较快地死亡，并且不能像其外底层对应物一样长时间增殖。在此，我们展示了表达基因的关键标记基因在不同细胞类型上随时间变化的情况下，顶层内翻的器官小体的增殖潜力大大降低，这一点可以通过免疫组织化学染色和嘧啶类似物EdU的结合来证明。同时，细胞死亡水平也增加。然而，这些现象不能被分化诱导来解释，因为各种细胞类型的关键标记基因的基因表达随时间不变。© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.

Apical-out intestinal organoids are a relatively simple method of gaining access to the apical cell surface and have faced increasing scientific interest over the last few years. Apical-out organoids can thus be used for disease modelling to compare differing effects on the basolateral versus the apical cell surface. However, these 'inside-out' organoids die relatively quickly and cannot be propagated as long as their basal-out counterparts. Here, we show that apical-out organoids have drastically reduced proliferative potential, as evidenced by immunohistochemical staining and the incorporation of the thymidine analogue EdU. At the same time, cell death levels are increased. Nevertheless, these phenomena cannot be explained by an induction of differentiation, as the gene expression of key marker genes for various cell types does not change over time.© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.