Long-lived keratin 15+ esophageal progenitor cells contribute to homeostasis and regeneration

Véronique Giroux, Ashley A. Lento, Mirazul Islam, Jason R. Pitarresi, Akriti Kharbanda, Kathryn E. Hamilton, Kelly A. Whelan, Apple Long, Ben Rhoades, Qiaosi Tang, Hiroshi Nakagawa, Christopher J. Lengner, Adam J. Bass, E. Paul Wileyo, Andres J. Klein-Szanto, Timothy C. Wang, Anil K. Rustgi

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The esophageal lumen is lined by a stratified squamous epithelium comprised of proliferative basal cells that differentiate while migrating toward the luminal surface and eventually desquamate. Rapid epithelial renewal occurs, but the specific cell of origin that supports this high proliferative demand remains unknown. Herein, we have described a long-lived progenitor cell population in the mouse esophageal epithelium that is characterized by expression of keratin 15 (Krt15). Genetic in vivo lineage tracing revealed that the Krt15 promoter marks a long-lived basal cell population able to self-renew, proliferate, and generate differentiated cells, consistent with a progenitor/stem cell population. Transcriptional profiling demonstrated that Krt15+ basal cells are molecularly distinct from Krt15- basal cells. Depletion of Krt15-derived cells resulted in decreased proliferation, thereby leading to atrophy of the esophageal epithelium. Further, Krt15+ cells were radioresistant and contributed to esophageal epithelial regeneration following radiation-induced injury. These results establish the presence of a long-lived and indispensable Krt15+ progenitor cell population that provides additional perspective on esophageal epithelial biology and the widely prevalent diseases that afflict this epithelium.

Original languageEnglish
Pages (from-to)2378-2391
Number of pages14
JournalJournal of Clinical Investigation
Volume127
Issue number6
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Fingerprint

Dive into the research topics of 'Long-lived keratin 15+ esophageal progenitor cells contribute to homeostasis and regeneration'. Together they form a unique fingerprint.

Cite this