Telocytes deliver essential Wnts directly to murine intestinal stem cells via synapse-like contacts.

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.