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Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon [bulk rna-seq]

ABSTRACT: Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon [bulk rna-seq]

PROVIDER: PRJNA1003423 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25569900_1.fastq.gz	Fastqsanger.gz
	SRR25569900_2.fastq.gz	Fastqsanger.gz
	SRR25569901_1.fastq.gz	Fastqsanger.gz
	SRR25569901_2.fastq.gz	Fastqsanger.gz
	SRR25569902_1.fastq.gz	Fastqsanger.gz

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Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon [scrna-seq]

Project description:Most organs have tissue resident immune cells that function during tissue development, homeostasis and disease. Human organoids, derived either from adult tissues or from pluripotent stem cells (PSCs), have been lacking these immune cells, which limits their utility to model many normal and disease processes. Here we describe that human PSC-derived colonic organoids (HCOs) co-develop a diverse population of immune cells. Comparisons to the developing human hematopoietic cells, demonstrate that HCO cultures developed hemogenic endothelium and erythromyeloid progenitors that undergo stereotypical steps in differentiation, resulting in the generation of macrophages. HCO macrophages acquired a transcriptional signature most similar to human fetal small and large intestine tissue-resident macrophages. Functional analyses demonstrate that HCO-macrophages modulate cytokine secretion in response to pro- and anti-inflammatory signals. In addition, macrophages were able to phagocytose and mount a robust response to pathogenic bacteria. In HCOs that were transplanted into mice, macrophages expanded 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 support the conclusion that hemogenic endothelium in HCOs gives rise to multipotent hematopoietic progenitors and functional tissue-resident macrophages.

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Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon [bulk rna-seq]

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

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

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Project description:Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon [scrna-seq]

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

Project description: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.

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

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