Xu Zebang, Xu Xinxin, Mi Yuling, Zhang Yuanyuan, Hong Qihua, Yang Bin, Wang Jiakun
Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China.
MoE Key Laboratory of Molecular Animal Nutrition, Zhejiang University, Hangzhou 310058, Zhejiang, China.
Stem Cells Int. 2025 Jul 11;2025:5105796. doi: 10.1155/sci/5105796. eCollection 2025.
Ruminants are of significant economic importance, and their unique digestive system features the rumen as a vital organ. The rumen is lined by stratified squamous epithelium, plays a crucial role in absorbing volatile fatty acids (VFAs) generated through microbial fermentation, thereby meeting the daily energy requirements of these animals. The maintenance of the rumen epithelium is a matter of concern. Here, we present compelling evidence that the hippo pathway effector yes-associated protein 1 (YAP) serves as a key regulator in maintaining rumen epithelial cells (RECs). Our findings indicate that rumen epithelial basal cells spontaneously undergo expansion and differentiation, ultimately forming organoids, and that the hippo signaling pathway is involved in regulating this process. Specifically, we demonstrate that YAP is indispensable for the initial specification and long-term maintenance of organoids. Activation of YAP promotes the growth and formation of these organoids, whereas inhibiting YAP hinders this developmental process. YAP activation exerts its effects by enhancing basal cells proliferation while simultaneously inhibiting differentiation. Conversely, YAP inhibition reduces the proliferation of basal cells. Notably, YAP activation promotes dedifferentiation of differentiated organoids. Moreover, YAP activation fosters intercellular tight junctions and strengthens cell-extracellular matrix interactions. In contrast, YAP inhibition reverses these features and leads to the disintegration of the organoids. Collectively, our data reveal the regulatory role of YAP in the rumen epithelium, which will help deepen the understanding of rumen development.
反刍动物具有重要的经济意义，其独特的消化系统以瘤胃作为重要器官。瘤胃内衬复层鳞状上皮，在吸收微生物发酵产生的挥发性脂肪酸（VFA）方面发挥关键作用，从而满足这些动物的日常能量需求。瘤胃上皮的维持是一个值得关注的问题。在此，我们提供了令人信服的证据，表明河马通路效应器Yes相关蛋白1（YAP）是维持瘤胃上皮细胞（REC）的关键调节因子。我们的研究结果表明，瘤胃上皮基底细胞会自发地进行增殖和分化，最终形成类器官，并且河马信号通路参与调节这一过程。具体而言，我们证明YAP对于类器官的初始特化和长期维持是不可或缺的。YAP的激活促进这些类器官的生长和形成，而抑制YAP则会阻碍这一发育过程。YAP激活通过增强基底细胞增殖同时抑制分化来发挥作用。相反，抑制YAP会减少基底细胞的增殖。值得注意的是，YAP激活促进已分化类器官的去分化。此外，YAP激活促进细胞间紧密连接并加强细胞与细胞外基质的相互作用。相比之下，抑制YAP会逆转这些特征并导致类器官解体。总体而言，我们的数据揭示了YAP在瘤胃上皮中的调节作用，这将有助于加深对瘤胃发育的理解。
