Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population.
Because the esophageal epithelium lacks a defined stem cell niche, it is unclear whether all basal epithelial cells in the adult esophagus are functionally equivalent. In this study, we showed that basal cells in the mouse esophagus contained a heterogeneous population of epithelial cells, similar to other rapidly cycling tissues such as the intestine or skin. Using a combination of cell-surface markers, we separated primary esophageal tissue into distinct cell populations that harbored differences in stem cell potential. We also used an in vitro 3D organoid assay to demonstrate that Sox2, Wnt, and bone morphogenetic protein signaling regulate esophageal self-renewal. Finally, we labeled proliferating basal epithelial cells in vivo to show differing cell-cycle profiles and proliferation kinetics. Based on our results, we propose that a nonquiescent stem cell population resides in the basal epithelium of the mouse esophagus.
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15219, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Aaron D
AD
DeWard
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15219, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Julie
J
Cramer
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15219, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA. Electronic address: lagasse@pitt.edu.
Eric
E
Lagasse
D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D004947:Esophagus / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D051153:Wnt Proteins