A New Study That Plots The Small Intestinal Epithelium Cell Altas

Recently, there is a study focusing on the small intestinal epithelium cell being published on Natural Journal, which is processed by a multicenter study team combined with researchers from the Broad Institute and the Massachusetts General Hospital.

In order to better understand the complex organization and function of small intestinal epithelium, as well as the diseases that affect it, took advantage of data from the mouse intestine and more than 53,000 cells from the intestinal organ models, performing a high-resolution gene-based census on the cells that make up the small intestinal epithelium. This census results include the first small intestine cell altas, which provides a reference for the study of a series of biological mechanisms affecting inflammatory bowel disease, small intestine cancer, celiac disease and food allergy, or involving the intestinal tract.

Besides, it can also help us get more acquainted with hormones and other signals produced by small intestinal epithelium, and provide with new clues about how the small intestinal epithelium should respond to different pathogens. Small intestinal epithelium, as a cell ecosystem, is one of the most versatile and most active tissues in the body, which is also one of the major interfaces between the body and the outside world.

The intestinal epithelium comes into contact with the immune system and intestinal microbiome which makes it become the main center of cellular connectivity, that’s why it affects a lot for us to understand the health and disease of intestinal. Researchers rely on single-cell RNA sequencing to conduct the survey, as a group of genomic technologies that identify specific gene expression profiles within a single cell, it assisted researchers to generate a total of 53,193 gene expression profiles of intestinal epithelial cells. With these data, they identified known cell types (such as gut epithelium, goblet cells, Paneth cells and plexiform cells), specific cell subtypes or populations (such as intestinal epithelial cells at different stages of maturation), and rare cell types (Such as M cells), as well as specific gene expression characteristics. They also assign known and new specific sensory molecules associated with each type of intestinal epithelial cell.

These data also reveal the existence of previously unrecognized cell subtypes and support the reclassification of known cell types. For example, the researchers unveiled a new test chemical called tuft cell that helps remind the immune system that the body suffers from an infection or other forms of damage that are regarded as a marker of immune cells previously. All of which will be helpful to alert allergens and invading parasites.

Researchers found that the gene expression of TSLP which can encode a cytokine known to be involved in epithelial-induced inflammation for a long time was limited to specific clusters of plexiform cells, suggesting that these recently described cells have an important "watchdog" effect. In addition, these data have shown that hormone-producing enteroendocrine cells (EECs) in the intestinal which are divided into different subgroups based on the insight that each EEC subpopulation produces only one hormone actually are able to produce a variety of hormones.

The researchers also plot their data along the length of the small intestine to different parts of the small intestine. For example, they found that EEC producing ghrelin tended to accumulate near the beginning of the small intestine (ie, the duodenum, besides the stomach). And those EECs that produce peptide YY (which promotes satiation) accumulate near the distal end of the small intestine (ileum).

In order to validate the practicability of this altas as a reference for small intestine disease research, the researchers investigated two models of intestinal infections: a Salmonella infection model and a model of infection of Heligmosomoides polygyrus.

By comparing these data with these reference censuses, the results show that the lining of the intestine significantly self-rebuilds to cope with the infection. Depending on the type of infectious lesion, certain cell types significantly increase or decrease in abundance. The expression profiles of many cells also vary significantly, including pathogen-specific changes.

In consideration of these reference cell census data, these researchers are excited to conduct further studies including those involving gastrointestinal disease models or gastrointestinal disorders, including Crohn's disease, ulcerative colitis, gastrointestinal cancer and food allergies, to identify gene expression, epithelial structure and functional changes that will provide new insights and opportunities for drug development.


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