Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Clinica Reina Fabiola, Oncativo 1248, Cordoba 5004, Argentina.
Carcinogenesis. 2015 Jan;36(1):25-31. doi: 10.1093/carcin/bgu221. Epub 2014 Oct 24.
Lgr5+ intestinal crypt base columnar cells function as stem cells whose progeny populate the villi, and Lgr5+ cells in which Apc is inactivated can give rise to tumors. Surprisingly, these Lgr5+ stem cell properties were abrogated by the lower dietary vitamin D and calcium in a semi-purified diet that promotes both genetically initiated and sporadic intestinal tumors. Inactivation of the vitamin D receptor in Lgr5+ cells established that compromise of Lgr5 stem cell function was a rapid, cell autonomous effect of signaling through the vitamin D receptor. The loss of Lgr5 stem cell function was associated with presence of Ki67 negative Lgr5+ cells at the crypt base. Therefore, vitamin D, a common nutrient and inducer of intestinal cell maturation, is an environmental factor that is a determinant of Lgr5+ stem cell functions in vivo. Since diets used in reports that establish and dissect mouse Lgr5+ stem cell activity likely provided vitamin D levels well above the range documented for human populations, the contribution of Lgr5+ cells to intestinal homeostasis and tumor formation in humans may be significantly more limited, and variable in the population, then suggested by published rodent studies.
Lgr5+ 肠隐窝基底柱状细胞作为干细胞发挥功能，其后代可填充于绒毛中，而 Apc 失活的 Lgr5+细胞可引发肿瘤。令人惊讶的是，这种 Lgr5+干细胞特性会被半纯化饮食中较低的维生素 D 和钙所破坏，而这种半纯化饮食可促进遗传引发和散发性肠肿瘤的发生。Lgr5+细胞中维生素 D 受体的失活表明，维生素 D 受体信号通路的损害是 Lgr5 干细胞功能的快速、细胞自主效应。Lgr5 干细胞功能的丧失与隐窝底部 Ki67 阴性 Lgr5+细胞的存在有关。因此，维生素 D 是一种常见的营养物质和肠道细胞成熟诱导剂，是决定 Lgr5+干细胞体内功能的环境因素。由于报道中用于建立和剖析小鼠 Lgr5+干细胞活性的饮食可能提供了远超人类群体记录范围的维生素 D 水平，因此与已发表的啮齿动物研究相比，Lgr5+细胞对人类肠道稳态和肿瘤形成的贡献可能受到显著限制，且在人群中存在差异。
