Isthmus Stem Cells Are the Origins of Metaplasia in the Gastric Corpus.
Isthmus Stem Cells Are the Origins of Metaplasia in the Gastric Corpus.
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DOI：
10.1016/j.jcmgh.2017.02.009
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发表时间：
2017-07
影响因子：
7.2
通讯作者：
Wang TC
中科院分区：
文献类型：
--
作者：
Hayakawa Y;Fox JG;Wang TC
在长寿的胃肠道干细胞中获得遗传/表观遗传突变导致癌症的发展，以及癌前病变，如化生和发育不良。在近端胃体中，这种从干细胞进展的模型已经得到了小鼠和人类研究的支持，显示出峡部的大量增殖和来自干细胞区域的突变细胞的克隆扩增。另一种理论认为胃上皮化生是由成熟的分化的主细胞引起的。尽管报道了急性损伤模型中主细胞的低水平增殖，但几乎没有证据表明主细胞重编程为长寿命干细胞，随着时间的推移持续提供后代。主要细胞转分化理论的关键缺陷包括急性SPEM的定义，化学试剂的主要细胞损伤作用，以及主要细胞谱系追踪的特异性。相比之下，现在有强有力的证据表明胃化生的干细胞起源反驳了转分化理论。在这里，我们简要回顾了胃化生的历史和定义，并详细概述了支持化生的干细胞起源的证据。
The acquisition of genetic/epigenetic mutations in long-lived gastrointestinal stem cells leads to the development of cancer, as well as precancerous lesions such as metaplasia and dysplasia. In the proximal stomach corpus, this model of progression from stem cells has been supported by studies in mice and human beings, showing abundant proliferation in the isthmus and clonal expansion of mutated cells from the stem cell region. An alternative theory proposes that gastric metaplasia arises from mature differentiated chief cells. Despite reports of low levels of proliferation in chief cells in acute injury models, there is little evidence for reprogramming of chief cells into long-lived stem cells that continuously supply progeny over time. Critical flaws in the chief cell transdifferentiation theory include the definition of acute SPEM, the chief cell-damaging effect of chemical reagents, and the specificity of chief cell lineage tracing. In contrast, there is now strong evidence regarding the stem cell origins of gastric metaplasia that refutes the transdifferentiation theory. Here, we briefly review the history and definition of gastric metaplasia, and outline in detail the evidence that supports the stem cell origin of metaplasia.