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

• Andreas E. Moor ^[1] ; Yotam Harnik ^[1] ; Shani Ben-Moshe ^[1]
  1. [1] Weizmann Institute of Science

     Weizmann Institute of Science

     Israel

     
• Localización: Cell, ISSN 0092-8674, Vol. 175, Nº. 4, 2018, págs. 1156-1167
• Idioma: inglés
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• Resumen

  • 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.