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A spatial expression atlas of the adult human proximal small intestine

Author

Listed:
  • Yotam Harnik

    (Weizmann Institute of Science)

  • Oran Yakubovsky

    (Weizmann Institute of Science
    Sheba Medical Center
    Tel Aviv University)

  • 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
    Sheba Medical Center)

  • 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
    Sheba Medical Center)

  • Niv Pencovich

    (Sheba Medical Center
    Tel Aviv University)

  • Ron Pery

    (Sheba Medical Center
    Tel Aviv University)

  • Dror S. Shouval

    (Tel Aviv University
    Schneider Children’s Medical Center of Israel)

  • Itay Tirosh

    (Weizmann Institute of Science)

  • Ido Nachmany

    (Sheba Medical Center
    Tel Aviv University)

  • Shalev Itzkovitz

    (Weizmann Institute of Science)

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.

Suggested Citation

  • 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 & Y, 2024. "A spatial expression atlas of the adult human proximal small intestine," Nature, Nature, vol. 632(8027), pages 1101-1109, August.
    • Handle: RePEc:nat:nature:v:632:y:2024:i:8027:d:10.1038_s41586-024-07793-3
    DOI: 10.1038/s41586-024-07793-3
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