Dclk1+ small intestinal epithelial tuft cells display the hallmarks of quiescence and self-renewal

Abstract

To date, no discrete genetic signature has been defined for isolated Dclk1⁺ tuft cells within the small intestine. Furthermore, recent reports on the functional significance of Dclk1⁺ cells in the small intestine have been inconsistent. These cells have been proposed to be fully differentiated cells, reserve stem cells, and tumor stem cells. In order to elucidate the potential function of Dclk1⁺ cells, we FACS-sorted Dclk1⁺ cells from mouse small intestinal epithelium using transgenic mice expressing YFP under the control of the Dclk1 promoter (Dclk1-CreER;Rosa26-YFP). Analysis of sorted YFP⁺ cells demonstrated marked enrichment (~6000 fold) for Dclk1 mRNA compared with YFP⁻ cells. Dclk1⁺ population display ~6 fold enrichment for the putative quiescent stem cell marker Bmi1. We observed significantly greater expression of pluripotency genes, pro-survival genes, and quiescence markers in the Dclk1⁺ population. A significant increase in self-renewal capability (14-fold) was observed in in vitro isolated Dclk1⁺ cells. The unique genetic report presented in this manuscript suggests that Dclk1⁺ cells may maintain quiescence, pluripotency, and metabolic activity for survival/longevity. Functionally, these reserve characteristics manifest in vitro, with Dclk1⁺ cells exhibiting greater ability to self-renew. These findings indicate that quiescent stem-like functionality is a feature of Dclk1-expressing tuft cells.