Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon
Summary
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.
| Authors | Múnera JO, Kechele DO, Bouffi C, Qu N, Jing R, Maity P, Enriquez JR, Han L, Campbell I, Mahe MM, McCauley HA, Zhang X, Sundaram N, Hudson JR, Zarsozo-Lacoste A, Pradhan S, Tominaga K, Sanchez JG, Weiss AA, Chatuvedi P, Spence JR, Hachimi M, North T, Daley GQ, Mayhew CN, Hu YC, Takebe T, Helmrath MA, Wells JM |
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| Journal | Cell stem cell |
| Publication Date | 2023 Nov 2;30(11):1434-1451.e9 |
| PubMed | 37922878 |
| PubMed Central | PMC10913028 |
| DOI | 10.1016/j.stem.2023.10.002 |