| First Author | Múnera JO | Year | 2023 |
| Journal | Cell Stem Cell | Volume | 30 |
| Issue | 11 | Pages | 1434-1451.e9 |
| PubMed ID | 37922878 | Mgi Jnum | J:342845 |
| Mgi Id | MGI:7561409 | Doi | 10.1016/j.stem.2023.10.002 |
| Citation | Munera JO, et al. (2023) Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon. Cell Stem Cell 30(11):1434-1451.e9 |
| abstractText | 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. |
