Ankenbauer, Katherine E.; Yang, Yilin; Chung, Chi-Yeh; Andrade, Leonardo R.; Novak, Sammy Weiser; Jarvis, Brenda; Ali Hanel, Wahida H.; Liu, Jiayue; Sarkisian, Victoria; Dani, Neil; Krystofiak, Evan; Hu, Gaizun; Ebrahim, Seham; Kachar, Bechara; Gong, Qizhi; Wahl, Geoffrey M.; Lau, Ken S.; Brown, Jeffrey W.; Manor, Uri; DelGiorno, Kathleen E. (2026).听.听Cellular and Molecular Gastroenterology and Hepatology, 20(6), 101742.听
This study explores the structure and function of聽tuft cells, a rare type of cell found in tissues like the intestine that help protect the body during infection, inflammation, and cancer by releasing signaling molecules such as cytokines and eicosanoids (chemicals involved in immune responses). Tuft cells are easily recognized by their distinctive surface made up of short, stiff projections called聽microvilli, which resemble the hair-like structures (stereocilia) on sensory cells in the ear. However, until now, it has been unclear whether these structures actually serve a sensory role. The researchers focused on a key gene regulator called聽POU2F3聽(a transcription factor, meaning it controls the activity of other genes) to understand how these microvilli are formed and maintained.
Using a combination of genetic analysis and imaging techniques, the team identified several genes controlled by POU2F3 that are shared between tuft cells and inner ear hair cells, including聽Pcdh20, which encodes a structural protein. Advanced microscopy showed that the PCDH20 protein is located within the microvilli of tuft cells and the stereocilia of hair cells. When the researchers reduced or removed this gene in mice, the microvilli in tuft cells became disorganized and less rigid, suggesting that PCDH20 is essential for maintaining their structure. Computer-based protein modeling further suggested that PCDH20 molecules may physically connect neighboring microvilli, helping keep them aligned and stable.
Overall, the findings show that Pcdh20 is directly regulated by POU2F3 and plays a crucial role in building the unique microvillar structure of tuft cells. The discovery that tuft cells share structural and potentially sensory components with inner ear hair cells raises the possibility that tuft cells may also have聽mechanosensory functions鈥攖hat is, they might be able to detect physical forces or movement鈥攕imilar to how hair cells in the ear detect sound.
Graphical Abstract