Research Overview by Dr. Katie Golden, MD: A single-cell survey of the small intestinal epithelium

The intestinal mucosa is home to the most diverse epithelial tissue in the body, but our current understanding of this cell population is limited. In a new study published by Haber in Nature, researchers apply next generation DNA sequencing, which allows for higher resolution investigation, to this heterogenous group of cells. The result is the discovery of new subtypes of intestinal epithelial cells, better characterization of their gene expression and function, and an opportunity to study how these cells respond to infection.

In this study, researchers use a single-cell RNA sequencing method to study the diversity and specific functions of gastrointestinal epithelial cells. Prior to this technology, investigators relied on previously defined cell markers to isolate and study cell populations, an inherently limited process,  akin to studying the color spectrum of a rainbow with glasses that only allowed for certain light frequencies. With this new technology, however, researchers were able to analyze the unique genetic expression of over 50,000 individual epithelial cells, and the result is a more precise understanding of the intestinal mucosa’s cell diversity and dynamic functions.

The application of single-cell sequencing to this specific population yielded a number of interesting results. For example, researchers were able to better characterize the gene transcription that determined the geographic fate and thus function of enterocytes (e.g. proximal versus distal intestine). They re-classified subtypes of enteroendocrine cells based on a more accurate description of their hormone expression. They identified two new subsets of tuft cells – chemosensory cells that line the gut – and interestingly found one of these subsets to express a specific immune marker that was formerly thought to be exclusive to haematopoietic cells. Finally, and perhaps most interesting, the investigators profiled the molecular responses of the epithelial cells to bacterial (Salmonella enterica) and parasitic helminth (Heligmosomoides polygyrus) infections. More specifically, they observed the upregulation of disease-specific cells and the restructuring of the epithelial barrier in response to these infections.

This paper provides an important step towards a more intimate understanding of the cellular dynamics of gastrointestinal epithelium, which in turn increases our potential to better understand of the small intestine’s response to infection, environmental changes, and disease.