Abstract

The intestinal epithelium forms the inner layer of the human intestine and serves a wide range of diverse functions. Its constant exposure to a vast amount of complex microbiota highlights the critical interface that this single-cell layer forms between the host and our environment. Importantly, the well-documented contribution of environmental factors towards the functional development of the human intestinal epithelium directly implies epigenetic mechanisms in orchestrating this complex interplay. The development of intestinal epithelial organoid culture systems that can be generated from human tissue provides researchers with unpresented opportunities to study functional aspects of human intestinal epithelial pathophysiology. In this brief review, we summarise existing evidence for the role of epigenetics in regulating intestinal epithelial cell function and highlight the great potential for human gut organoids as translational research tools to investigate these mechanisms in vitro.

Highlights

  • The intestinal epithelium serves a large variety of diverse functions including absorption of nutrients and water as well as forming a critical barrier to the environment [1]

  • The ability to mediate exposure to environmental factors into potentially stable alterations of cellular function is a hallmark of all epigenetic mechanisms [2]

  • Their involvement in regulating cellular function of the intestinal epithelium during development and in healthy homeostasis follows as a logical conclusion

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Summary

Introduction

The intestinal epithelium serves a large variety of diverse functions including absorption of nutrients and water as well as forming a critical barrier to the environment [1]. The ability to mediate exposure to environmental factors into potentially stable alterations of cellular function is a hallmark of all epigenetic mechanisms [2] Their involvement in regulating cellular function of the intestinal epithelium during development and in healthy homeostasis follows as a logical conclusion. Given the complexity of environmental factors that might contribute to shaping the intestinal epithelial epigenome in vivo, a reductionist approach may be beneficial in order to identify underlying mechanisms In this respect, the development of three-dimensional organoid models, which closely resemble the in vivo situation, has provided unprecedented opportunities for scientists to investigate fundamental aspects of cell biology. Work from our group and others have started to investigate the use of human IEOs as translational research tools to explore the role of epigenetic mechanisms in GI development, healthy homeostasis, and related diseases [30, 34]

Epigenetics in Human Intestinal Epithelial Cell Development
Epigenetics in Intestinal Epithelial Homeostasis
Epigenetics in IEC Malfunction and Disease
Future Perspectives
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