Greicius Gediminas, Mittermeier Lorenz, Liang Ruanyi, Sigmundsson Kristmundur, Chan Yarn Kit, Liao Pei-Ju, Ludwig Alexander, Virshup David M
Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore.
Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore.
Dev Cell. 2025 Jul 19. doi: 10.1016/j.devcel.2025.06.040.
Spatial and temporal control of Wnt delivery to the intestinal stem cell niche regulates intestinal homeostasis. Telocytes, specialized stromal cells with characteristic long, thin cytoplasmic protrusions, produce essential Wnts for the development and maintenance of this niche. However, how Wnts travel from telocytes to stem cells in the gut remains unclear. Fluorescence and electron microscopy of murine telocytes co-cultured with intestinal organoids identified specialized telocyte extensions that transport and locally secrete Wnts on microvesicles and make intimate contacts with epithelial cells, reminiscent of neuronal contact-based signaling. Investigating the potential role of synapse-forming and plasma membrane-associated platform proteins, we found that depletion of either KANK1 or Liprins from telocytes markedly reduced their filopodia, compromised WNT2 presentation to epithelial cells, and impaired telocyte-dependent organoid growth. Characteristic telocyte structures facilitate Wnt delivery to the intestinal stem cell niche via synapse-like contacts.
Wnt信号传递至肠道干细胞龛的时空控制调节肠道内稳态。端细胞是具有特征性长而细的细胞质突起的特殊基质细胞，可产生维持该龛发育和维持所必需的Wnt信号。然而，Wnt信号如何从端细胞传递至肠道干细胞仍不清楚。对与肠道类器官共培养的小鼠端细胞进行荧光和电子显微镜观察，发现了特殊的端细胞延伸结构，这些结构可在微泡上运输并局部分泌Wnt信号，并与上皮细胞形成紧密接触，这让人联想到基于神经元接触的信号传导。通过研究形成突触和与质膜相关的平台蛋白的潜在作用，我们发现端细胞中KANK1或Liprin的缺失会显著减少其丝状伪足，损害WNT2向上皮细胞的呈递，并损害端细胞依赖的类器官生长。特征性的端细胞结构通过类似突触的接触促进Wnt信号传递至肠道干细胞龛。
