A spatial expression atlas of the adult human proximal small intestine

成果类型:
Article
署名作者:
Harnik, Yotam; Yakubovsky, Oran; Hoefflin, Rouven; Novoselsky, Roy; Halpern, Keren Bahar; Barkai, Tal; Kohanim, Yael Korem; Egozi, Adi; Golani, Ofra; Addadi, Yoseph; Kedmi, Merav; Haran, Tal Keidar; Levin, Yishai; Savidor, Alon; Keren-Shaul, Hadas; Mayer, Chen; Pencovich, Niv; Pery, Ron; Shouval, Dror S.; Tirosh, Itay; Nachmany, Ido; Itzkovitz, Shalev
署名单位:
Weizmann Institute of Science; Tel Aviv University; Chaim Sheba Medical Center; Tel Aviv University; Chaim Sheba Medical Center; Tel Aviv University; Yale University; Weizmann Institute of Science; Hebrew University of Jerusalem; Hadassah University Medical Center; Weizmann Institute of Science; Chaim Sheba Medical Center; Tel Aviv University; Tel Aviv University
刊物名称:
Nature
ISSN/ISSBN:
0028-4476
DOI:
10.1038/s41586-024-07793-3
发表日期:
2024-08-29
页码:
1101-+
关键词:
serrated adenoma cells proteins immunity signals MODEL
摘要:
The mouse small intestine shows profound variability in gene expression along the crypt-villus axis(1,2). 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 gamma delta 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.