AsianScientist (Sep. 17, 2025) – Scientists from Duke-NUS Medical School and Nanyang Technological University in Singapore have shed new light on the movement of Wnts, a class of signaling proteins vital for multicellular life. Disruption of their timely and specific delivery to target cells have been linked to cancers and other disorders.
The adult intestine, in particular, is a hub of constant cellular renewal, where stem cells depend on Wnts released from nearby support cells to specialize into the gut lining. Because Wnts are water-repelling and sticky, how they reach stem cells when needed has been a mystery.
In a recent study published in Developmental Cell, the research team from Singapore took a closer look at telocytes—the support cells thought to supply Wnts and characterized by curiously long, thin extensions that weave beneath the intestinal epithelium. What they found upends our understanding of how the gut maintains and repairs itself.
“We discovered that these signals aren’t just drifting through tissue. They’re being delivered with surprising precision from the niche to the stem cells by specialized cells or telocytes—changing the way we think about cellular communication in the gut,” said study co-author David Vishnup, a professor at Duke-NUS and director of the Programme in Cancer and Stem Cell Biology.
In the lab, the team co-cultured telocytes with intestinal organoids—miniature guts grown in a dish—and imaged them using high-resolution fluorescence and electron microscopy. The telocytes stretched long telopodes, branching into finer filopodia that wrapped around the organoids and touched individual stem cells. Wnts were loaded into vesicles and sent along these extensions to be secreted right at the points of contact.
The researchers noticed that the internal “tracks” ferrying Wnt-filled vesicles and the junctions between telocytes and stem cells resembled the way neurons transmit signals at synapses. Sure enough, telocytes carried Liprin-α2 and KANK1—neuronal proteins that support branch-like structures and assemble docking sites where cargo-carrying vesicles are guided for their targeted release. When Liprin-α2 and KANK1 were removed, the telocytes formed fewer filopodia, their Wnt transport machinery broke down and organoid growth faltered.
“Sometimes when you study the basics closely, you uncover something transformative,” said Gediminas Greicius, an assistant professor and principal scientist at Duke-NUS’s Programme in Cancer and Stem Cell Biology, who led the study. “This system of targeted signaling was hiding in plain sight, and now that we see it, it reshapes our understanding of the biology of stem cells in the gut.”
The team’s discovery could also inspire new directions for treating conditions driven by faulty Wnt signaling, like inflammatory bowel disease (IBD) and colon cancer.
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Source: Duke-NUS Medical School ; Image: Shutterstock
This article can be found at Telocytes deliver essential Wnts directly to murine intestinal stem cells via synapse-like contacts.
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