Researcher ORCID Identifier
Date of Submission
Open Access Senior Thesis
Bachelor of Arts
The cells of the small intestine (SI) epithelium are constantly renewing by way of intestinal stem cells (ISCs), which are located in the crypts of the SI. Tuft cells are a cell type of the small intestine that initiate type 2 immune responses upon worm infection, by signaling ILC2s (type 2 innate lymphoid cells) to produce cytokines such as IL-13 that mount an immune response and promote tuft cell production until infection is cleared. However, many questions remain regarding what signals drive tuft cell generation and maturation during homeostasis. The Ras guanine nucleotide exchange factor, RasGRP1, lies downstream of the EGFR and suppresses proliferative SOS1 signals. Preliminary work from the Roose lab has identified RasGRP1 as a novel regulator of tuft cell generation. Specifically, mice deficient for RasGRP1 have about half as many tuft cells as wild type mice. Therefore, in order to test if EGFR/RasGRP1 play a mechanistic role in tuft cell generation, a multi-antibody spectral flow panel was developed with the capability of detecting all epithelial cell types in the mouse SI. We made organoids from the crypts of the small intestine of mice, and treated them with increasing concentrations of the EGFR, gefitinib, recombinant IL-13, and a combination of both. Via spectral flow cytometry and immunostaining, we found that the combination of EGFRi and IL-13 together results in the greatest amount of tuft cell differentiation. These results suggest that tuft cell production is regulated by EGFR signaling in the adult mouse small intestine.
Duflock, Annabelle, "EGFR Signaling Regulates Tuft Cell Generation in the Adult Mouse Small Intestine" (2024). CMC Senior Theses. 3427.
Available for download on Tuesday, December 03, 2024