Introduction and Objective: C414A-CRY1 transgenic mice (TG) develop diabetes due to SASP-like phenotypes in β-cells. We demonstrated that mucinous intra-islet ductal cells (IIDCs) expressing TFF2, that is known as a marker of spasmolytic polypeptide-expressing metaplasia (SPEM) in the stomach, emerge age-dependently in TG. Reportedly, acinar to ductal metaplasia (ADM) occurs through a process similar to SPEM. To explore the characters of IIDCs and their origins, in this study we examined the expression of SPEM/ADM markers in both β-cells and IIDCs in TG.Methods: By immunostaining the degrees of the expression of IIDCs were judged as strong or negative/weak-positive for SPEM/ADM markers (GKN3, AGR2, AQP5 and GSII-lectin). Markers for Tuft cells (DCLK1, acetylated α-tubulin and TRPM5) were also examined. The positional relationship between GKN3-expressing β-cells and IIDCs was examined.Results: IIDCs reacted to GSII-lectin. GKN3 and AGR2 were expressed in IIDCs. AQP5-positive cells were barely observed in IIDCs. GKN3-expressing partially degranulated β-cells appeared in the regions of adjacent to IIDCs. GKN3 expressing atypical β-cells were located as a constituent of the epithelium of IIDCs as well. Regarding Tuft cell markers, both DCLK1 and acetylated α-tubulin double-positive cells located in IIDCs. TRPM5-expressing cells were also observed in IIDCs. These results indicate that Tuft cells are constituent elements of IIDCs.Conclusion: Our results suggest that IIDCs arise through mechanisms partially common to SPEM/ADM under SASP-like microenvironment in islets. The results indicating the emergence of Tuft cells in the IIDCs reinforce the notion. The GKN3-expressing β-cells might be transitional cells undertaking transdifferentiation toward IIDCs, indicating a possibility that IIDCs could be originated from β-cells.
S. Okano: None. A. Yasui: None. S. Kanno: None. Y. Sasaki: None. K. Satoh: None. M. Igarashi: None. O. Nakajima: None.
Grants-in-Aid for Scientific Research (24K11670); Tohoku University Institute of Development, Aging and Cancer
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