Krt19⁺/Lgr5^- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine

Authors

Samuel Asfaha, Columbia UniversityFollow
Yoku Hayakawa, Columbia University
Ashlesha Muley, Columbia University
Sarah Stokes, Columbia University
Trevor A. Graham, Barts and The London School of Medicine and Dentistry
Russell E. Ericksen, Columbia University
Christoph B. Westphalen, Columbia University
Johannes Von Burstin, Klinikum rechts der Isar der Technischen Universität München
Teresa L. Mastracci, Columbia University
Daniel L. Worthley, Columbia University
Chandhan Guha, Albert Einstein College of Medicine of Yeshiva University
Michael Quante, Klinikum rechts der Isar der Technischen Universität München
Anil K. Rustgi, Penn Medicine
Timothy C. Wang, Columbia University

Document Type

Article

Publication Date

6-4-2015

Journal

Cell Stem Cell

Volume

16

Issue

6

First Page

627

Last Page

638

URL with Digital Object Identifier

10.1016/j.stem.2015.04.013

Abstract

Epithelium of the colon and intestine are renewed every 3 days. In the intestine there are at least two principal stem cell pools. The first contains rapid cycling crypt-based columnar (CBC) Lgr5+ cells, and the second is composed of slower cycling Bmi1-expressing cells at the +4 position above the crypt base. In the colon, however, the identification of Lgr5- stem cell pools has proven more challenging. Here, we demonstrate that the intermediate filament keratin-19 (Krt19) marks long-lived, radiation-resistant cells above the crypt base that generate Lgr5+ CBCs in the colon and intestine. In colorectal cancer models, Krt19+ cancer-initiating cells are also radioresistant, while Lgr5+ stem cells are radiosensitive. Moreover, Lgr5+ stem cells are dispensable in both the normal and neoplastic colonic epithelium, as ablation of Lgr5+ stem cells results in their regeneration from Krt19-expressing cells. Thus, Krt19+ stem cells are a discrete target relevant for cancer therapy.