大多数器官都有组织驻留的免疫细胞。人类类器官缺乏这些免疫细胞，这限制了它们在模拟许多正常和疾病过程中的效用。在这里，我们描述了多能干细胞衍生的人类结肠类器官（HCO）共同发育出多种免疫细胞群，包括造血内皮（HE）样细胞和红骨髓祖细胞，它们经历典型的分化步骤，从而产生功能性巨噬细胞。 HCO 巨噬细胞获得了类似于人类胎儿小肠和大肠组织驻留巨噬细胞的转录特征。 HCO巨噬细胞响应促炎和抗炎信号调节细胞因子分泌，并且能够吞噬病原菌并对病原菌产生强烈反应。当移植到小鼠体内时，HCO巨噬细胞保留在结肠类器官组织内，与结肠上皮建立了密切的联系，并且不会被宿主骨髓来源的巨噬细胞取代。这些研究表明，HCO 中的 HE 会产生多能造血祖细胞和功能性组织驻留巨噬细胞。版权所有 © 2023 Elsevier Inc. 保留所有权利。

Most organs have tissue-resident immune cells. Human organoids lack these immune cells, which limits their utility in modeling many normal and disease processes. Here, we describe that pluripotent stem cell-derived human colonic organoids (HCOs) co-develop a diverse population of immune cells, including hemogenic endothelium (HE)-like cells and erythromyeloid progenitors that undergo stereotypical steps in differentiation, resulting in the generation of functional macrophages. HCO macrophages acquired a transcriptional signature resembling human fetal small and large intestine tissue-resident macrophages. HCO macrophages modulate cytokine secretion in response to pro- and anti-inflammatory signals and were able to phagocytose and mount a robust response to pathogenic bacteria. When transplanted into mice, HCO macrophages were maintained within the colonic organoid tissue, established a close association with the colonic epithelium, and were not displaced by the host bone-marrow-derived macrophages. These studies suggest that HE in HCOs gives rise to multipotent hematopoietic progenitors and functional tissue-resident macrophages.Copyright © 2023 Elsevier Inc. All rights reserved.