TY - JOUR
T1 - Long-lived keratin 15+ esophageal progenitor cells contribute to homeostasis and regeneration
AU - Giroux, Véronique
AU - Lento, Ashley A.
AU - Islam, Mirazul
AU - Pitarresi, Jason R.
AU - Kharbanda, Akriti
AU - Hamilton, Kathryn E.
AU - Whelan, Kelly A.
AU - Long, Apple
AU - Rhoades, Ben
AU - Tang, Qiaosi
AU - Nakagawa, Hiroshi
AU - Lengner, Christopher J.
AU - Bass, Adam J.
AU - Wileyo, E. Paul
AU - Klein-Szanto, Andres J.
AU - Wang, Timothy C.
AU - Rustgi, Anil K.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85020234712&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000402620800031&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1172/JCI88941
DO - 10.1172/JCI88941
M3 - Article
C2 - 28481227
SN - 0021-9738
VL - 127
SP - 2378
EP - 2391
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 6
ER -