Tissue Responses to Shiga Toxin in Human Intestinal Organoids.

Cellular and Molecular Gastroenterology and Hepatology
Suman PradhanHeather A McCauley

Abstract

Shiga toxin (Stx)-producing Escherichia coli (eg, O157:H7) infection produces bloody diarrhea, while Stx inhibits protein synthesis and causes the life-threatening systemic complication of hemolytic uremic syndrome. The murine intestinal tract is resistant to O157:H7 and Stx, and human cells in culture fail to model the complex tissue responses to intestinal injury. We used genetically identical, human stem cell-derived intestinal tissues of varying complexity to study Stx toxicity in vitro and in vivo. In vitro susceptibility to apical or basolateral exposure to Stx was assessed using human intestinal organoids (HIOs) derived from embryonic stem cells, or enteroids derived from multipotent intestinal stem cells. HIOs contain a lumen, with a single layer of differentiated epithelium surrounded by mesenchymal cells. Enteroids only contain epithelium. In vivo susceptibility was assessed using HIOs, with or without an enteric nervous system, transplanted into mice. Stx induced necrosis and apoptotic death in both epithelial and mesenchymal cells. Responses that require protein synthesis (cellular proliferation and wound repair) also were observed. Epithelial barrier function was maintained even after epithelial cell death was seen...Continue Reading

Citations

Sep 10, 2020·International Journal of Molecular Sciences·Bénédicte Allam-NdoulAlain Veilleux
Dec 30, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bo LiAgostino Pierro

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Datasets Mentioned

BETA
GSE144633

Methods Mentioned

BETA
Fluorescence
confocal microscopy

Software Mentioned

edgeR
TopHat
Bioconductor
ImageJ

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