title: 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.
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Oklahoma Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Parthasarathy
authors.initials: P
authors.lastname: Chandrakesan
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA.
authors.forename: Randal
authors.initials: R
authors.lastname: May
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Qu
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Weygant
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Vivian E
authors.initials: VE
authors.lastname: Taylor
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Oklahoma Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Naushad
authors.initials: N
authors.lastname: Ali
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Sripathi M
authors.initials: SM
authors.lastname: Sureban
authors.affiliation: Klinikum rechts der Isar, II. Medizinische Klinik, Technische Universität München, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Qante
authors.affiliation: Department of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Bronze
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Stephenson Oklahoma Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA.|COARE Biotechnology, Oklahoma City, OK, USA.
authors.forename: Courtney W
authors.initials: CW
authors.lastname: Houchen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D000089742:Doublecortin-Like Kinases; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D007421:Intestine, Small / Q000166:cytology* / Q000502:physiology; D008136:Longevity; D051379:Mice; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D000089742:Doublecortin-Like Kinases; C485525:Dclk1 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: Dclk1; pluripotency; quiescence; self-renewal