The adult Drosophila posterior midgut is maintained by pluripotent stem cells
The adult Drosophila posterior midgut is maintained by pluripotent stem cells
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DOI：
10.1038/nature04333
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发表时间：
2006-01-26
期刊：
影响因子：
64.8
通讯作者：
Spradling, A
中科院分区：
文献类型：
--
作者：
Ohlstein, B;Spradling, A
脊椎动物和无脊椎动物的消化系统在发育、细胞组成和遗传控制方面表现出广泛的相似性（1）。果蝇的中肠是典型的：肠上皮细胞构成了肠上皮单层的大部分，但也散布着产生蛋白质的肠内分泌细胞（2-4）。人类（和小鼠）肠细胞不断由干细胞补充，其失调可能是一些常见消化系统疾病和癌症的基础（5）。相比之下，在果蝇的肠道中还没有描述过干细胞，果蝇的肠道细胞被认为是相对稳定的（6-7）。在这里，我们使用谱系标记显示，成年果蝇后中肠细胞不断补充了一个独特的人口肠道干细胞（ISCs）。在脊椎动物中，ISC是多能的，并且需要Notch信号传导来产生适当比例的肠内分泌细胞（8）。Notch也是ISC子细胞分化所必需的，这一作用在脊椎动物中尚未得到解决。与先前表征的干细胞不同，干细胞位于含有特定伴侣基质细胞的壁龛中（9，10），ISCs仅与基底膜、分化的肠上皮细胞及其最近的子细胞邻接。果蝇肠道干细胞与脊椎动物肠道干细胞具有惊人的相似性，这将有助于对正常和异常肠道功能进行遗传分析。
Vertebrate and invertebrate digestive systems show extensive similarities in their development, cellular makeup and genetic control(1). The Drosophila midgut is typical: enterocytes make up the majority of the intestinal epithelial monolayer, but are interspersed with hormone-producing enteroendocrine cells(2-4). Human ( and mouse) intestinal cells are continuously replenished by stem cells, the misregulation of which may underlie some common digestive diseases and cancer(5). In contrast, stem cells have not been described in the intestines of flies, and Drosophila intestinal cells have been thought to be relatively stable(6-7). Here we use lineage labelling to show that adult Drosophila posterior midgut cells are continuously replenished by a distinctive population of intestinal stem cells (ISCs). As in vertebrates, ISCs are multipotent, and Notch signalling is required to produce an appropriate fraction of enteroendocrine cells(8). Notch is also required for the differentiation of ISC daughter cells, a role that has not been addressed in vertebrates. Unlike previously characterized stem cells, which reside in niches containing a specific partner stromal cell(9,10), ISCs adjoin only the basement membrane, differentiated enterocytes and their most recent daughters. The identification of Drosophila intestinal stem cells with striking similarities to their vertebrate counterparts will facilitate the genetic analysis of normal and abnormal intestinal function.