Spatial Reconstruction of Single Enterocytes Uncovers Broad Zonation along the Intestinal Villus Axis
Spatial Reconstruction of Single Enterocytes Uncovers Broad Zonation along the Intestinal Villus Axis
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DOI：
10.1016/j.cell.2018.08.063
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发表时间：
2018-11-01
期刊：
影响因子：
64.5
通讯作者：
Itzkovitz, Shalev
中科院分区：
文献类型：
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作者：
Moor, Andreas E.;Harnik, Yotam;Itzkovitz, Shalev
肠上皮是由重复的隐窝-绒毛单元组成的高度结构化的组织。肠细胞执行吸收各种营养物质的不同任务，同时保护身体免受恶劣的富含细菌的环境的影响。目前尚不清楚这些任务是否是空间分区沿着绒毛轴。在这里，我们提取了一个大的面板的里程碑基因的特点是转录组学的激光捕获显微切割绒毛段，并利用它的单细胞空间重建，揭示了广泛的带状肠上皮细胞功能沿着绒毛。我们发现绒毛底部的肠上皮细胞以微生物组依赖的方式表达抗菌基因程序。他们接下来转移到不同绒毛隔室中碳水化合物，肽和脂肪吸收机制的顺序表达。最后，它们在绒毛尖端诱导Cd 73免疫调节程序。我们的方法可以用来发现在其他器官的分区模式时，缺乏里程碑基因的先验知识。
The intestinal epithelium is a highly structured tissue composed of repeating crypt-villus units. Enterocytes perform the diverse tasks of absorbing a wide range of nutrients while protecting the body from the harsh bacterium-rich environment. It is unknown whether these tasks are spatially zonated along the villus axis. Here, we extracted a large panel of landmark genes characterized by transcriptomics of laser capture microdissected villus segments and utilized it for single-cell spatial reconstruction, uncovering broad zonation of enterocyte function along the villus. We found that enterocytes at villus bottoms express an anti-bacterial gene program in a microbiome-dependent manner. They next shift to sequential expression of carbohydrates, peptides, and fat absorption machineries in distinct villus compartments. Finally, they induce a Cd73 immune-modulatory program at the villus tips. Our approach can be used to uncover zonation patterns in other organs when prior knowledge of landmark genes is lacking.