Dclk1+ small intestinal epithelial tuft cells display the hallmarks of quiescence and self-renewal
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Parthasarathy Chandrakesan1,2, Randal May1,3, Dongfeng Qu1,3, Nathaniel Weygant1, Vivian E. Taylor1, James D. Li1, Naushad Ali1,2, Sripathi M. Sureban1, Michael Qante4, Timothy C. Wang5, Michael S. Bronze1, Courtney W. Houchen1,2,3,6
1Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
2Stephenson Oklahoma Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
3Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA
4Klinikum rechts der Isar, II. Medizinische Klinik, Technische Universität München, Munich, Germany
5Department of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY, USA
6COARE Biotechnology, Oklahoma City, OK, USA
Courtney W. Houchen, e-mail: Courtneyfirstname.lastname@example.org
Parthasarathy Chandrakesan, e-mail: email@example.com
Keywords: Dclk1, self-renewal, pluripotency, quiescence
Received: July 15, 2015 Accepted: August 19, 2015 Published: September 02, 2015
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.
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