美国辛辛那提儿童医院医疗中心James M. Wells和Jorge O. Múnera共同合作，近期取得重要工作进展。他们研究发现，人多能干细胞来源的结肠类器官和人胎儿结肠中功能性常驻巨噬细胞的发育。相关研究成果2023年11月2日在线发表于《细胞—干细胞》杂志上。

据介绍，大多数器官都有组织固有的免疫细胞。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作用。

研究人员描述了多能干细胞来源的人类结肠类器官（HCO）共同发育不同的免疫细胞群，包括造血内皮（HE）样细胞和红系祖细胞，它们在分化过程中经历典型步骤，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常驻巨噬细胞的转录特征。HCO巨噬细胞调节细胞因子分泌以响应促炎和抗炎信号，并能够吞噬病原菌并对其产生强烈反应。当移植到小鼠体内时，HCO巨噬细胞维持在结肠类器官组织内，与结肠上皮建立密切联系，并且不会被宿主骨髓来源的巨噬细胞取代。

总之，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。

附：英文原文

Title: Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon

Author: Jorge O. Múnera, Daniel O. Kechele, Carine Bouffi, Na Qu, Ran Jing, Pritiprasanna Maity, Jacob R. Enriquez, Lu Han, Ian Campbell, Maxime M. Mahe, Heather A. McCauley, Xinghao Zhang, Nambirajan Sundaram, Jonathan R. Hudson, Adrian Zarsozo-Lacoste, Suman Pradhan, Kentaro Tominaga, J. Guillermo Sanchez, Alison A. Weiss, Praneet Chatuvedi, Jason R. Spence, Mariam Hachimi, Trista North, George Q. Daley, Christopher N. Mayhew, Yueh-Chiang Hu, Takanori Takebe, Michael A. Helmrath, James M. Wells

Issue&Volume: 2023/11/02

Abstract: 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.

DOI: 10.1016/j.stem.2023.10.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00364-8