近日，丹麦哥本哈根大学教授Kim B. Jensen团队探明了肠道隐窝几何形状的工程化揭示了YAP1依赖的胎儿至成体转变。相关论文于2026年2月12日发表在《细胞—干细胞》杂志上。

利用复制隐窝样几何形状的工程支架，研究团队建立了一个机器人平台，用于指导胎儿肠细胞的形态发生和分化为成熟的工程组织，模仿它们在体内的对应体。从机制上讲，组织成熟是由细胞拥挤驱动的，导致YAP1激活降低。在工程组织和发育中的无主题肠中调节YAP信号可以改变上皮谱系的规格。这些发现揭示了一种将组织结构与细胞命运转变联系起来的几何依赖机制。他们的工作为肠道发育的建模提供了一个平台，并为改进肠道疾病的干细胞分化方案和再生策略提供了见解。

据了解，在形态发生过程中，肠道经历了显著的结构重塑，从一个简单的未成熟上皮管转变为一个复杂的隐窝绒毛结构，形成成熟的细胞类型。然而，这些结构变化和上皮细胞成熟之间的关系仍然是个谜。

附：英文原文

Title: Engineered intestinal crypt geometry uncovers YAP1-dependent fetal-to-adult transition

Author: Martti Maimets, Mikhail Nikolaev, Cecilia Lvkvist, Fabien Bertillot, Hjalte List Larsen, Raul Bardini Bressan, Antonios Georgantzoglou, Nikolce Gjorevski, Eirini Filidou, Maureen Zylner, Stine Lind Hansen, Astrid M. Baattrup, Isidora Banjac, Jordi Guiu, Sara A. Wickstrm, Matthias P. Lutolf, Kim B. Jensen

Issue&Volume: 2026-02-12

Abstract: During morphogenesis, the intestine undergoes significant structural remodeling, transitioning from a simple tube of immature epithelium into a complex crypt-villus architecture housing mature cell types. However, the relationship between these structural changes and epithelial maturation has remained enigmatic. Using engineered scaffolds that replicate crypt-like geometries, we establish a robust platform for guiding the morphogenesis and differentiation of fetal intestinal cells into mature engineered tissues that mimic their in vivo counterparts. Mechanistically, tissue maturation is driven by cell crowding, leading to reduced YAP1 activation. Modulating YAP signaling in both engineered tissues and the developing mouse intestine alters epithelial lineage specification. These findings uncover a geometry-dependent mechanism that links tissue architecture to cell fate transitions. Our work provides a platform for modeling aspects of intestinal development and offers insights for refining stem cell differentiation protocols and regenerative strategies for intestinal disorders.

DOI: 10.1016/j.stem.2026.01.006

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(26)00029-9