9 March 2021, Singapore – Dr Florent Ginhoux, Dr Ng Lai Guan, and Dr Melissa Ng from A*STAR’s Singapore Immunology Network (SIgN), together with collaborators from Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China have found a new subset of gut cells that organise the intestinal stem cell niche, which is important for tissue repair. The study was published in the scientific journal, Nature on 3 March 2021.
1 https://www.healthhub.sg/a-z/diseases-and-conditions/24/colorectalcancer2 https://www.healthxchange.sg/digestive-system/irritable-bowel-syndrome/inflammatory-bowel-disease-ibd-iritable-bowel-syndrome-ibs-difference
These gut cells protect the colon from acute injury via the ROS–MAP3K2–KLF2–RSPO1 axis and hence are termed MAP3K2-regulated intestinal stromal cells (MRISC). Future investigation of MRISCs for their potential roles in restraining intestinal inflammation and pathology as well as their identification in human tissues and how to mobilise them could offer new therapeutic strategies to treat inflammatory bowel disease and colitis-associated colorectal cancer.
Colorectal cancer is cancer of the colon (the main part of the large intestine) and the rectum (the passageway connecting the colon to the anus). It is the top killer in Singapore, affecting more than 1,200 cases each year1. Inflammatory bowel disease (IBD) can strike at any age, although most sufferers are diagnosed between the ages of 20 and 40 years2.
Intestinal stromal cells are known to modulate the propagation and differentiation of intestinal stem cells. However, the precise cellular and molecular mechanisms by which this diverse stromal cell population maintains tissue homeostasis and repair are poorly understood. A subset of intestinal stromal cells, named MAP3K2-regulated intestinal stromal cells (MRISCs) show that they are the primary cellular source of the WNT agonist R-spondin 1 following intestinal injury in mice. Their results identify MRISCs as a key component of an intestinal stem cell niche that specifically depends on MAP3K2 to augment WNT signalling for the regeneration of damaged intestine.
Dr Florent Ginhoux, Senior Principal Investigator, SIgN and co-last author of the study said, “The identification of such population of cells that can modulate the gut stem cell niche offers new therapeutical perspectives for gut disorders and we are going to investigate their presence and functions in human tissues.”
Professor Bing Su, Director, Shanghai Institute of Immunology and co-last author of the study added, “Our study also opens new avenues for studying the roles of these stromal cell subsets not only in gastrointestinal system, but also in many other systems for example immune or neuron systems, both in animal models and in human disease settings.”
More information on the study, “MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche” can be found via the team’s published paper in Nature: https://doi.org/10.1038/s41586-021-03283-y