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

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

Cell stem cell (2023-11-06)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-CLDN18 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-CD163 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution