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Spatial Reconstruction of Single Enterocytes Uncovers Broad Zonation along the Intestinal Villus Axis

2018; Cell Press; Volume: 175; Issue: 4 Linguagem: Inglês

10.1016/j.cell.2018.08.063

1097-4172

Andreas E. Moor, Yotam Harnik, Shani Ben‐Moshe, Efi E. Massasa, Milena Rozenberg, Raya Eilam, Keren Bahar Halpern, Shalev Itzkovitz,

Cancer Cells and Metastasis

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.