Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains

Rachel K. Zwick, Petr Kasparek, Brisa Palikuqi, Sara Viragova, Laura Weichselbaum, Christopher S. McGinnis, Kara L. McKinley, Asoka Rathnayake, Dedeepya Vaka, Vinh Nguyen, Coralie Trentesaux, Efren Reyes, Alexander R. Gupta, Zev J. Gartner, Richard M. Locksley, James M. Gardner, Shalev Itzkovitz, Dario Boffelli, Ophir D. Klein

Research output: Contribution to journalArticlepeer-review


A key aspect of nutrient absorption is the exquisite division of labour across the length of the small intestine, with individual nutrients taken up at different proximal:distal positions. For millennia, the small intestine was thought to comprise three segments with indefinite borders: the duodenum, jejunum and ileum. By examining the fine-scale longitudinal transcriptional patterns that span the mouse and human small intestine, we instead identified five domains of nutrient absorption that mount distinct responses to dietary changes, and three regional stem cell populations. Molecular domain identity can be detected with machine learning, which provides a systematic method to computationally identify intestinal domains in mice. We generated a predictive model of transcriptional control of domain identity and validated the roles of Ppar-δ and Cdx1 in patterning lipid metabolism-associated genes. These findings represent a foundational framework for the zonation of absorption across the mammalian small intestine.

Original languageEnglish
Pages (from-to)250-262
Number of pages13
JournalNature Cell Biology
Issue number2
StatePublished Online - 6 Feb 2024

All Science Journal Classification (ASJC) codes

  • Cell Biology


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