AUTHOR=Hishida Tomoaki , Vazquez-Ferrer Eric , Hishida-Nozaki Yuriko , Takemoto Yuto , Hatanaka Fumiyuki , Yoshida Kei , Prieto Javier , Sahu Sanjeeb Kumar , Takahashi Yuta , Reddy Pradeep , O’Keefe David D. , Rodriguez Esteban Concepcion , Knoepfler Paul S. , Nuñez Delicado Estrella , Castells Antoni , Campistol Josep M. , Kato Ryuji , Nakagawa Hiroshi , Izpisua Belmonte Juan Carlos TITLE=Myc Supports Self-Renewal of Basal Cells in the Esophageal Epithelium JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.786031 DOI=10.3389/fcell.2022.786031 ISSN=2296-634X ABSTRACT=

It is widely believed that cellular senescence plays a critical role in both aging and cancer, and that senescence is a fundamental, permanent growth arrest that somatic cells cannot avoid. Here we show that Myc plays an important role in self-renewal of esophageal epithelial cells, contributing to their resistance to cellular senescence. Myc is homogeneously expressed in basal cells of the esophageal epithelium and Myc positively regulates their self-renewal by maintaining their undifferentiated state. Indeed, Myc knockout induced a loss of the undifferentiated state of esophageal epithelial cells resulting in cellular senescence while forced MYC expression promoted oncogenic cell proliferation. A superoxide scavenger counteracted Myc knockout-induced senescence, therefore suggesting that a mitochondrial superoxide takes part in inducing senescence. Taken together, these analyses reveal extremely low levels of cellular senescence and senescence-associated phenotypes in the esophageal epithelium, as well as a critical role for Myc in self-renewal of basal cells in this organ. This provides new avenues for studying and understanding the links between stemness and resistance to cellular senescence.