Song Andrew T, Sindeaux Renata H M, Li Yuanyi, Affia Hicham, Agnihotri Tapan, Leclerc Severine, van Vliet Patrick Piet, Colas Mathieu, Guimond Jean-Victor, Patey Natalie, Feulner Lara, Joyal Jean-Sebastien, Haddad Elie, Barreiro Luis, Andelfinger Gregor
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada; Department of Anatomy and Cell Biology, McGill University, Montréal, QC, Canada.
Centre de Recherche, CHU Sainte-Justine, Montréal, QC, Canada; Meakins Christie Laboratories, Department of Medicine, Department of Microbiology and Immunology, Department of Pathology Research Institute of McGill University Health Centre, Montréal, QC, Canada.
Cell Rep. 2024 Jan 23;43(1):113616. doi: 10.1016/j.celrep.2023.113616. Epub 2023 Dec 26.
Macrophages populate the embryo early in gestation, but their role in development is not well defined. In particular, specification and function of macrophages in intestinal development remain little explored. To study this event in the human developmental context, we derived and combined human intestinal organoid and macrophages from pluripotent stem cells. Macrophages migrate into the organoid, proliferate, and occupy the emerging microanatomical niches of epithelial crypts and ganglia. They also acquire a transcriptomic profile similar to that of fetal intestinal macrophages and display tissue macrophage behaviors, such as recruitment to tissue injury. Using this model, we show that macrophages reduce glycolysis in mesenchymal cells and limit tissue growth without affecting tissue architecture, in contrast to the pro-growth effect of enteric neurons. In short, we engineered an intestinal tissue model populated with macrophages, and we suggest that resident macrophages contribute to the regulation of metabolism and growth of the developing intestine.
巨噬细胞在妊娠早期就出现在胚胎中，但其在发育过程中的作用尚未明确界定。特别是，巨噬细胞在肠道发育中的特化和功能仍鲜有人探索。为了在人类发育背景下研究这一事件，我们从多能干细胞中衍生并组合了人类肠道类器官和巨噬细胞。巨噬细胞迁移到类器官中，增殖并占据上皮隐窝和神经节新出现的微观解剖学龛位。它们还获得了与胎儿肠道巨噬细胞相似的转录组特征，并表现出组织巨噬细胞行为，如对组织损伤的募集。使用这个模型，我们发现与肠神经元的促生长作用相反，巨噬细胞减少间充质细胞中的糖酵解并限制组织生长，而不影响组织结构。简而言之，我们构建了一个充满巨噬细胞的肠道组织模型，并且我们认为驻留巨噬细胞有助于调节发育中肠道的代谢和生长。
