Quiescent gastric stem cells maintain the adult Drosophila stomach

Quiescent gastric stem cells maintain the adult Drosophila stomach
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DOI:
10.1073/pnas.1109794108
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发表时间:
2011-10-25
影响因子:
11.1
通讯作者:
Micchelli, Craig A.
Micchelli, Craig A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Strand, Marie;Micchelli, Craig A.

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成年果蝇铜细胞区或“胃”是中肠的高酸性区室,pH < 3。在这个区域,一个专门的组类似于哺乳动物胃壁细胞的泌酸细胞已被确定由一个独特的超微结构和铜金属硫蛋白荧光。然而,维持成人中肠的酸分泌“铜细胞”的自我平衡机制尚未得到研究。在这里,我们结合联合收割机细胞谱系追踪和遗传分析,以探讨胃上皮细胞维持的机制。我们的研究表明,一个分子可识别的多能,自我更新的胃干细胞(GSSC)的人口产生的酸分泌铜细胞,间质细胞,和胃的肠内分泌细胞。我们的试验表明,GSSC在很大程度上是静止的,但可以被诱导再生胃上皮细胞,以响应环境的挑战。最后,遗传分析表明,成人GSSC的维持依赖于Wnt信号传导。GSSC谱系在果蝇中的特点,与哺乳动物惊人的相似性,将推进胃的稳态和致病过程的研究。
The adult Drosophila copper cell region or "stomach" is a highly acidic compartment of the midgut with pH < 3. In this region, a specialized group of acid-secreting cells similar to mammalian gastric parietal cells has been identified by a unique ultrastructure and by copper-metallothionein fluorescence. However, the homeostatic mechanism maintaining the acid-secreting "copper cells" of the adult midgut has not been examined. Here, we combine cell lineage tracing and genetic analysis to investigate the mechanism by which the gastric epithelium is maintained. Our investigation shows that a molecularly identifiable population of multipotent, self-renewing gastric stem cells (GSSCs) produces the acid-secreting copper cells, interstitial cells, and enteroendocrine cells of the stomach. Our assays demonstrate that GSSCs are largely quiescent but can be induced to regenerate the gastric epithelium in response to environmental challenge. Finally, genetic analysis reveals that adult GSSC maintenance depends on Wnt signaling. Characterization of the GSSC lineage in Drosophila, with striking similarities to mammals, will advance the study of both homeostatic and pathogenic processes in the stomach.