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

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 transpl

SUBMITTER: Munera JO 

PROVIDER: S-EPMC10913028 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature