以色列魏茨曼科学研究所Shalev Itzkovitz研究团队绘制出成人人体近端小肠的空间表达图谱。相关论文于2024年8月7日在线发表在《自然》杂志上。

研究人员利用空间转录组学、空间蛋白质组学和单分子荧光原位杂交技术，重建了成人人体近端小肠的综合空间表达图谱。研究人员描述了上皮、间质和免疫细胞类型的区域化表达和细胞类型分布。研究人员发现，迁移的肠上皮细胞在绒毛底部进行脂滴组装和铁摄取，而在绒毛尖端则进行乳糜微粒生物合成和铁释放。

绒毛尖端细胞具有促免疫性，招募γδ T细胞和巨噬细胞到尖端，这与小鼠中的免疫抑制作用形成对比。研究人员还发现，人类小肠包含丰富的锯齿状和分支的绒毛，这些绒毛主要分布在圆形褶皱的顶部。该研究提供了一个详细的资源，有助于理解成人人体小肠的生物学。

据介绍，小鼠小肠在隐窝-绒毛轴上表现出显著的基因表达变异。然而，成人人体肠道是否存在类似的空间异质性仍不清楚。

附：英文原文

Title: A spatial expression atlas of the adult human proximal small intestine

Author: Harnik, Yotam, Yakubovsky, Oran, Hoefflin, Rouven, Novoselsky, Roy, Bahar Halpern, Keren, Barkai, Tal, Korem Kohanim, Yael, Egozi, Adi, Golani, Ofra, Addadi, Yoseph, Kedmi, Merav, Keidar Haran, Tal, Levin, Yishai, Savidor, Alon, Keren-Shaul, Hadas, Mayer, Chen, Pencovich, Niv, Pery, Ron, Shouval, Dror S., Tirosh, Itay, Nachmany, Ido, Itzkovitz, Shalev

Issue&Volume: 2024-08-07

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.

DOI: 10.1038/s41586-024-07793-3

Source: https://www.nature.com/articles/s41586-024-07793-3