Dataset Information

Bulk RNA-seq of human colonic organoids treated with IFNγ and TNF

ABSTRACT: Human intestinal epithelial organoids derived from non-IBD patients were used to investigate transcriptional responses associated with inflammatory cytokine-induced epithelial cell death. Organoids were stimulated with IFNγ and TNF to model inflammatory injury observed in IBD. Bulk RNA sequencing was performed to characterise cytokine-driven gene expression programs associated with inducible nitric oxide synthase (iNOS) activation, epithelial stress responses, mitochondrial apoptosis, and inflammatory signalling pathways. Comparative transcriptomic analyses identified inflammatory and cell death-associated gene signatures induced by IFNγ/TNF treatment and revealed molecular pathways linked to epithelial injury in human intestinal organoids. These data provide a resource for understanding how inflammatory cytokines regulate epithelial cell death and transcriptional remodelling in the intestinal epithelium during IBD-associated inflammation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE330696 | GEO | 2026/09/03

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Treatment of inflammatory bowel disease (IBD) is challenging, with a series of available drugs each helping only a fraction of patients. Patients may face time-consuming drug trials while the disease is active, thus there is an unmet need for biomarkers and assays to predict drug effect. It is well known that the intestinal epithelium is an important factor in disease pathogenesis, exhibiting physical, biochemical and immunologic driven barrier dysfunctions. One promising test system to study effects of existing or emerging IBD treatments targeting intestinal epithelial cells (IECs) is intestinal organoids (“mini-guts”). However, the fact that healthy intestinal epithelium is in a physiologically hypoxic state has largely been neglected, and studies with intestinal organoids are mainly performed at oxygen concentration of 20%. We hypothesized that lowering the incubator oxygen level from 20% to 2% would recapitulate better the in vivo physiological environment of colonic epithelial cells and enhance the translational value of intestinal organoids as a drug testing platform. In the present study we examine the effects of the key IBD cytokines and drug targets TNF/IL17 on human colonic organoids (colonoids) under atmospheric (20%) or reduced (2%) O2. We show that colonoids derived from both healthy controls and IBD-patients are viable and responsive to IBD-relevant cytokines at 2% oxygen. Because chemokine release is one of the important immunoregulatory traits of the epithelium that may be fine-tuned by IBD-drugs, we also examined chemokine expression and release at different oxygen concentrations. We show that chemokine responses to TNF/IL17 in organoids display similarities to inflamed epithelium in IBD-patients. However, inflammation-associated genes induced by TNF/IL17 were attenuated at low oxygen concentration. We detected substantial oxygen-dependent differences in gene expression in untreated as well as TNF/IL17 treated colonoids in all donors. Further, for some of the IBD-relevant cytokines differences between colonoids from healthy controls and IBD patients were more pronounced in 2% O2 than 20% O2. Our results strongly indicate that an oxygen concentration similar to the in vivo epithelial cell environment is of essence in experimental pharmacology.

Dataset Information

Bulk RNA-seq of human colonic organoids treated with IFNγ and TNF

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets