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

Cell. 2018 Nov 1;175(4):1156-1167.e15. doi: 10.1016/j.cell.2018.08.063. Epub 2018 Sep 27.


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.

Keywords: metabolism; mucosal immunology; single-cell transcriptomics; spatial transcriptomics; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Movement
  • Enterocytes / cytology
  • Enterocytes / metabolism*
  • Enterocytes / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Single-Cell Analysis
  • Transcriptome*