A spatial expression atlas of the adult human proximal small intestine

Yotam Harnik, Oran Yakubovsky, Rouven Hoefflin, Roy Novoselsky, Keren Bahar Halpern, Tal Barkai, Yael Korem Kohanim, Adi Egozi, Ofra Golani, Yoseph Addadi, Merav Kedmi, Tal Keidar Haran, Yishai Levin, Alon Savidor, Hadas Keren-Shaul, Chen Mayer, Niv Pencovich, Ron Pery, Dror S. Shouval, Itay Tirosh, Ido Nachmany and Shalev Itzkovitz ()
Additional contact information
Yotam Harnik: Weizmann Institute of Science
Oran Yakubovsky: Weizmann Institute of Science
Rouven Hoefflin: Weizmann Institute of Science
Roy Novoselsky: Weizmann Institute of Science
Keren Bahar Halpern: Weizmann Institute of Science
Tal Barkai: Weizmann Institute of Science
Yael Korem Kohanim: Yale University School of Medicine
Adi Egozi: Weizmann Institute of Science
Ofra Golani: Weizmann Institute of Science
Yoseph Addadi: Weizmann Institute of Science
Merav Kedmi: Weizmann Institute of Science
Tal Keidar Haran: Hadassah Hebrew University Medical Center
Yishai Levin: Weizmann Institute of Science
Alon Savidor: Weizmann Institute of Science
Hadas Keren-Shaul: Weizmann Institute of Science
Chen Mayer: Tel Aviv University
Niv Pencovich: Sheba Medical Center
Ron Pery: Sheba Medical Center
Dror S. Shouval: Tel Aviv University
Itay Tirosh: Weizmann Institute of Science
Ido Nachmany: Sheba Medical Center
Shalev Itzkovitz: Weizmann Institute of Science

Nature, 2024, vol. 632, issue 8027, 1101-1109

Abstract: Abstract The mouse small intestine shows profound variability in gene expression along the crypt–villus axis1,2. Whether similar spatial heterogeneity exists in the adult human gut remains unclear. Here we use spatial transcriptomics, spatial proteomics and single-molecule fluorescence in situ hybridization to reconstruct a comprehensive spatial expression atlas of the adult human proximal small intestine. We describe zonated expression and cell type representation for epithelial, mesenchymal and immune cell types. We find that migrating enterocytes switch from lipid droplet assembly and iron uptake at the villus bottom to chylomicron biosynthesis and iron release at the tip. Villus tip cells are pro-immunogenic, recruiting γδ T cells and macrophages to the tip, in contrast to their immunosuppressive roles in mouse. We also show that the human small intestine contains abundant serrated and branched villi that are enriched at the tops of circular folds. Our study presents a detailed resource for understanding the biology of the adult human small intestine.

Date: 2024
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DOI: 10.1038/s41586-024-07793-3

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