Tripotent Lgr5 stem cells in the posterior tongue generate lingual, taste, and salivary gland lineages

Laurens H. G. Verweij, Seok-Young Kim, Dimitrios Laskaris, Lin Lin, Gijs J. F. van Son, Femke C. A. S. Ringnalda, Harry Begthel, Ravian L. van Ineveld, Chris Winkel, Jay P. Slack, Anne C. Rios, Karin Sanders, Jacco van Rheenen, Marc van de Wetering and Hans Clevers ()
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Laurens H. G. Verweij: The Princess Maxima Center for Pediatric Oncology
Seok-Young Kim: The Princess Maxima Center for Pediatric Oncology
Dimitrios Laskaris: Netherlands Cancer Institute, Division of Molecular Pathology, Oncode Institute
Lin Lin: Royal Netherlands Academy of Arts and Sciences and University Medical Center, Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center
Gijs J. F. van Son: The Princess Maxima Center for Pediatric Oncology
Femke C. A. S. Ringnalda: The Princess Maxima Center for Pediatric Oncology
Harry Begthel: Royal Netherlands Academy of Arts and Sciences and University Medical Center, Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center
Ravian L. van Ineveld: The Princess Maxima Center for Pediatric Oncology
Chris Winkel: Flavors, Givaudan Nederland
Jay P. Slack: Department of Science + Technology, Givaudan Flavors Corp
Anne C. Rios: The Princess Maxima Center for Pediatric Oncology
Karin Sanders: The Princess Maxima Center for Pediatric Oncology
Jacco van Rheenen: Netherlands Cancer Institute, Division of Molecular Pathology, Oncode Institute
Marc van de Wetering: The Princess Maxima Center for Pediatric Oncology
Hans Clevers: The Princess Maxima Center for Pediatric Oncology

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract The circumvallate papillae and foliate papillae of the posterior tongue contain taste buds in close proximity to specialized salivary glands, known as von Ebner glands. The developmental relationship between taste buds and these salivary glands has been suggested but remains largely unexplored at postnatal and adult stages. Lineage tracing studies in mice have revealed that Lgr5 marks taste bud stem cells. Here, we report single-cell RNA sequencing of the entire circumvallate and foliate papillae of mice, providing a transcriptional atlas of cells from tongue surface epithelium, taste buds, and the associated and non-associated salivary glands. We unveil a developmental trajectory in which taste buds, the associated salivary glands, and the non-taste tongue surface epithelium originate from a common Lgr5 cell. We confirm this tripotency at the clonal level in vitro and with multicolor lineage tracing in vivo. Thus, the circumvallate and foliate papillae harbor chemosensory units composed of taste bud and salivary gland cells derived from the same parental Lgr5-positive stem cell.

Date: 2025
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DOI: 10.1038/s41467-025-65140-0

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