Physiological and stem cell compartmentalization within the Drosophila midgut.
Physiological and stem cell compartmentalization within the Drosophila midgut.
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DOI：
10.7554/elife.00886
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发表时间：
2013-08-27
期刊：
影响因子：
7.7
通讯作者：
Spradling AC
中科院分区：
文献类型：
--
作者：
Marianes A;Spradling AC
果蝇中肠的整个长度由表面相似的多能肠干细胞维持，这些干细胞根据组织需求产生新的肠上皮细胞和肠内分泌细胞。我们发现中肠沿其前后轴显示出显着的区域分化。至少十个不同的子区域在细胞形态、生理学和数百个可能具有组织功能的基因的表达方面有所不同。干细胞的行为和基因表达也存在区域差异，这表明它们有助于中肠亚特化。克隆分析表明，干细胞仅在所测试的六个边界之一处产生位于其自身亚区域之外的后代，这表明中肠亚区域类似于参与组织发育的细胞区室。通过破坏 Notch 信号传导产生的肿瘤优先出现在三个亚区域，并且肿瘤细胞似乎也尊重区域边界。因此，表面上相似的肠道干细胞在细胞产生、基因表达和产生肿瘤的能力方面存在区域差异。 DOI：http://dx.doi.org/10.7554/eLife.00886.001 体内的许多细胞随着时间的推移而积累磨损，其中一部分细胞总是接近生命的终点。然而，在某些组织中，干细胞可以分裂成子细胞，然后子细胞分化并取代受损的细胞。与胚胎干细胞不同，这些“成体组织干细胞”通常仅分化为几种相关细胞类型，但它们产生替代细胞的能力使组织保持正常功能。在这里，玛丽亚内斯和斯普拉德林研究了一种存在于果蝇中肠中的成体干细胞，称为肠干细胞。中肠是果蝇消化的主要部位，其功能与哺乳动物的小肠非常相似。这种组织是一个长管，里面排列着两种类型的细胞：消化细胞和激素产生细胞。这些细胞类型由数千个明显相似的肠道干细胞维持，长期以来人们一直认为干细胞通过响应同一组信号在整个中肠中产生细胞。然而，某些消化过程（例如特定营养素的分解或吸收）仅发生在肠道的特定部分。例如，在果蝇中，肠道中部的一个区域被酸化，可能像一个额外的胃一样。在果蝇和哺乳动物中，铁主要在胃之后的肠道区域被吸收。这些功能上的区域差异导致中肠细胞如何产生和替换的不确定性。马里亚内斯和斯普拉德林现在根据对组织细胞和干细胞的详细研究表明，中肠至少包含十个以特定顺序出现的子区域。这些分区中的细胞具有独特的特征，包括形状、大小和内容物（例如，碳水化合物或营养素的储存）。每个子区域似乎在消化过程中执行特定的功能，并且这些子区域中的细胞还转录反映它们在分解或储存各种营养物质中的作用的基因。有趣的是，大多数分区中的干细胞是不同的，并且不会分化为相邻分区的细胞。这些分区的癌症发病率也有所不同：当所有十个分区的干细胞中的特定信号受到抑制时，仅在三个分区中形成侵袭性肿瘤，并且肿瘤细胞不会跨入邻近的分区。这些观察结果可能为未来对哺乳动物小肠的研究提供信息，并提高我们对其对癌症和其他疾病的易感性的了解。 DOI：http://dx.doi.org/10.7554/eLife.00886.002
The Drosophila midgut is maintained throughout its length by superficially similar, multipotent intestinal stem cells that generate new enterocytes and enteroendocrine cells in response to tissue requirements. We found that the midgut shows striking regional differentiation along its anterior-posterior axis. At least ten distinct subregions differ in cell morphology, physiology and the expression of hundreds of genes with likely tissue functions. Stem cells also vary regionally in behavior and gene expression, suggesting that they contribute to midgut sub-specialization. Clonal analyses showed that stem cells generate progeny located outside their own subregion at only one of six borders tested, suggesting that midgut subregions resemble cellular compartments involved in tissue development. Tumors generated by disrupting Notch signaling arose preferentially in three subregions and tumor cells also appeared to respect regional borders. Thus, apparently similar intestinal stem cells differ regionally in cell production, gene expression and in the ability to spawn tumors. DOI: http://dx.doi.org/10.7554/eLife.00886.001 Many cells in the body accumulate wear and tear over time, and a fraction of them are always nearing the end of their lives. However, in some tissues there are stem cells that can divide into daughter cells which then differentiate and replace the damaged cells. Unlike embryonic stem cells, these ‘adult tissue stem cells’ normally differentiate into only a few related cell types, but their ability to produce replacement cells keeps the tissue functioning normally. Here, Marianes and Spradling have investigated a type of adult stem cell, known as intestinal stem cells, that resides in the midgut of fruit flies. The midgut is the major site of digestion in fruit flies, and functions much like the small intestine in mammals. This tissue is a long tube that is lined with two types of cells: digestive cells and hormone-producing cells. These cell types are maintained by thousands of apparently similar intestinal stem cells, and it has long been thought that the stem cells give rise to cells throughout the midgut by responding to the same set of signals. However, certain digestive processes—such as the breakdown or uptake of particular nutrients—are known to occur only in a specific portion of the intestine. For example, in fruit flies, a region in the middle of the intestine is acidified, and may act like an extra stomach. And in both fruit flies and mammals, iron is taken up mostly in the area of the gut just after the stomach. These regional differences in function have led to uncertainty over how midgut cells both arise and are replaced. Marianes and Spradling now show, based on a detailed study of tissue cells and stem cells, that the midgut contains at least ten subregions that occur in a specific order. The cells in these subregions have distinct features, including shape, size and contents (e.g., stores of carbohydrates or nutrients). Each subregion appears to perform specific functions during digestion, and the cells in these subregions also transcribe genes that reflect their roles in breaking down or storing various nutrients. Interestingly, the stem cells in most subregions are distinct, and do not differentiate into the cells from adjacent subregions. The subregions also differ in their incidence of cancer: when a particular signal was inhibited in stem cells in all ten subregions, aggressive tumors formed in only three subregions and the tumor cells did not cross into neighboring subregions. These observations may inform future studies of the mammalian small intestine and improve our understanding of its susceptibility to cancer and other diseases. DOI: http://dx.doi.org/10.7554/eLife.00886.002