Paediatrics Publications

Title

Dclk1 Defines Quiescent Pancreatic Progenitors that Promote Injury-Induced Regeneration and Tumorigenesis

Authors

C. Benedikt Westphalen, Klinikum der Universität München
Yoshihiro Takemoto, Columbia University Irving Medical Center
Takayuki Tanaka, Columbia University Irving Medical Center
Marina Macchini, Columbia University Irving Medical Center
Zhengyu Jiang, Columbia University Irving Medical Center
Bernhard W. Renz, Klinikum der Universität München
Xiaowei Chen, Columbia University Irving Medical Center
Steffen Ormanns, Klinikum der Universität München
Karan Nagar, Columbia University Irving Medical Center
Yagnesh Tailor, Columbia University Irving Medical Center
Randal May, University of Oklahoma
Youngjin Cho, Columbia University Irving Medical Center
Samuel Asfaha, Columbia University Irving Medical CenterFollow
Daniel L. Worthley, Columbia University Irving Medical Center
Yoku Hayakawa, Columbia University Irving Medical Center
Aleksandra M. Urbanska, Columbia University Irving Medical Center
Michael Quante, Klinik und Poliklinik für Innere Medizin II, Technische Universität München
Maximilian Reichert, Klinik und Poliklinik für Innere Medizin II, Technische Universität München
Joshua Broyde, Columbia University Irving Medical Center
Prem S. Subramaniam, Columbia University Irving Medical Center
Helen Remotti, Columbia University Irving Medical Center
Gloria H. Su, Columbia University Irving Medical Center
Anil K. Rustgi, Penn Medicine
Richard A. Friedman, Columbia University Irving Medical Center
Barry Honig, Columbia University Irving Medical Center
Andrea Califano, Columbia University Irving Medical Center
Courtney W. Houchen, University of Oklahoma
Kenneth P. Olive, Columbia University Irving Medical Center
Timothy C. Wang, Columbia University Irving Medical Center

Document Type

Article

Publication Date

4-7-2016

Journal

Cell Stem Cell

Volume

18

Issue

4

First Page

441

Last Page

455

URL with Digital Object Identifier

10.1016/j.stem.2016.03.016

Abstract

The existence of adult pancreatic progenitor cells has been debated. While some favor the concept of facultative progenitors involved in homeostasis and repair, neither a location nor markers for such cells have been defined. Using genetic lineage tracing, we show that Doublecortin-like kinase-1 (Dclk1) labels a rare population of long-lived, quiescent pancreatic cells. In vitro, Dclk1+ cells proliferate readily and sustain pancreatic organoid growth. In vivo, Dclk1+ cells are necessary for pancreatic regeneration following injury and chronic inflammation. Accordingly, their loss has detrimental effects after cerulein-induced pancreatitis. Expression of mutant Kras in Dclk1+ cells does not affect their quiescence or longevity. However, experimental pancreatitis converts Kras mutant Dclk1+ cells into potent cancer-initiating cells. As a potential effector of Kras, Dclk1 contributes functionally to the pathogenesis of pancreatic cancer. Taken together, these observations indicate that Dclk1 marks quiescent pancreatic progenitors that are candidates for the origin of pancreatic cancer.

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