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J Pathol ; 248(2): 179-190, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30689202

RESUMEN

In the mammalian stomach, the isthmus has been considered as a stem cell zone. However, various locations and proliferative activities of gastric stem cells have been reported. We focused here on the stem cell marker Bmi1, a polycomb group protein, aiming to elucidate the characteristics of Bmi1-expressing cells in the stomach and to examine their stem cell potential. We investigated the Bmi1-expressing cell lineage in Bmi1-CreERT; Rosa26-YFP, LacZ or Rosa26-Confetti mice. We examined the in vivo and ex vivo effects of Bmi1-expressing cell ablation by using Bmi1-CreERT; Rosa26-iDTR mice. The Bmi1 lineage was also traced during regeneration after high-dose tamoxifen-, irradiation- and acetic acid-induced mucosal injuries. In the lineage-tracing experiments using low-dose tamoxifen, Bmi1-expressing cells in the isthmus of the gastric antrum and corpus provided progeny bidirectionally, towards both the luminal and basal sides over 6 months. In gastric organoids, Bmi1-expressing cells also provided progeny. Ablation of Bmi1-expressing cells resulted in impaired gastric epithelium in both mouse stomach and organoids. After high-dose tamoxifen-induced gastric mucosal injury, Bmi1-expressing cell lineages expanded and fully occupied all gastric glands of the antrum and the corpus within 7 days after tamoxifen injection. After irradiation- and acetic acid-induced gastric mucosal injuries, Bmi1-expressing cells also contributed to regeneration. In conclusion, Bmi1 is a gastric stem cell marker expressed in the isthmus of the antrum and corpus. Bmi1-expressing cells have stem cell potentials, both under physiological conditions and during regeneration after gastric mucosal injuries. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Asunto(s)
Complejo Represivo Polycomb 1/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Antro Pilórico/metabolismo , Células Madre/metabolismo , Ácido Acético , Animales , Biomarcadores/metabolismo , Diferenciación Celular , Linaje de la Célula , Proliferación Celular , Modelos Animales de Enfermedad , Fluorouracilo/toxicidad , Regulación del Desarrollo de la Expresión Génica , Humanos , Ratones Transgénicos , Complejo Represivo Polycomb 1/genética , Proteínas Proto-Oncogénicas/genética , Antro Pilórico/efectos de los fármacos , Antro Pilórico/embriología , Antro Pilórico/efectos de la radiación , Regeneración , Transducción de Señal , Células Madre/efectos de los fármacos , Células Madre/efectos de la radiación , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Tamoxifeno/toxicidad
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