Abstract
The single-layered, simple epithelium of the gastro-intestinal tract controls nutrient uptake, coordinates our metabolism and shields us from pathogens. Despite its seemingly simple architecture, the intestinal lining consists of highly distinct cell populations that are continuously renewed by the same stem cell population. The need to maintain balanced diversity of cell types in an unceasingly regenerating tissue demands intricate mechanisms of spatial or temporal cell fate control. Recent advances in single-cell sequencing, spatio-temporal profiling and organoid technology have shed new light on the intricate micro-structure of the intestinal epithelium and on the mechanisms that maintain it. This led to the discovery of unexpected plasticity, zonation along the crypt-villus axis and new mechanism of self-organization. However, not only the epithelium, but also the underlying mesenchyme is distinctly structured. Several new studies have explored the intestinal stroma with single cell resolution and unveiled important interactions with the epithelium that are crucial for intestinal function and regeneration. In this review, we will discuss these recent findings and highlight the technologies that lead to their discovery. We will examine strengths and limitations of each approach and consider the wider impact of these results on our understanding of the intestine in health and disease.
Highlights
As a single-layered columnar epithelium, the cell lining that covers the digestive tract appears deceptively simple
In the following paragraph we look beyond the field of intestinal biology and identify techniques and applications that could be useful to deepen our understanding of the gut
It comes in the form of trans-differentiation, as intestinal cell populations change their function in response to environmental stimuli and their position along the crypt-villus axis, and in the form of de-differentiation, when regenerative capacities are exhausted
Summary
As a single-layered columnar epithelium, the cell lining that covers the digestive tract appears deceptively simple. The epithelium and the underlying mesenchyme is exquisitely structured This is necessary to protect stem cells from the harsh environment inside the intestinal lumen, to optimize nutrient uptake and to maintain a seamless barrier that protects against mechanical stress, low pH and pathogen invasion. These diverse requirements led to the evolution of crypt and villus domains, which support regeneration and nutrient uptake respectively. Intestinal Structure and Plasticity sheet is in continuous motion and moves up to half a millimeter per day Despite this movement, the general spatial organization in the epithelium remains static. We will highlight recent findings and discuss the advantages and disadvantages of the new methods and technologies that uncovered the full extent of structured diversity in the intestine
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