A team of scientists at the Center for Vascular Research, within the Institute for Basic Science (IBS, South Korea) has identified new subsets of gut connective cells, which are crucial for lymphatic growth. Their new findings have been published in Nature Communications.
Researchers were able to demonstrate that the regulatory proteins YAP/TAZ in villi's connective cells—the intestinal stromal cells—play a role in the growth of nearby lacteals. In mice with an abnormal hyperactivation of YAP/TAZ, they observed atypical sprouting of lacteals and impaired dietary fat uptake. "The lacteals in these mice looked like tridents, which is very intriguing since we did not manipulate the lacteals themselves, but the surrounding cells," says Hong Seon Pyo, first co-author of this study.
Further analysis showed that intestinal stromal cells belong to several subtypes, with distinct gene expression and localization within the villi. Among these subsets, three newly identified populations secrete VEGF-C upon YAP/TAZ activation—VEGF-C is an essential molecule for lymphatic growth. "We were very surprised to see such heterogeneity in a cell population that was considered homogeneous," explains Yang Myung Jin, first co-author.
Their findings also include evidence that mechanical force and osmotic stress regulate YAP/TAZ activity in stromal cells. Through mechanical stimulation, YAP/TAZ becomes activated in the intestinal stromal cells, which then releases VEGF-C and accounts for lacteal growth. Cho Hyunsoo, first co-author of this study notes, "This result implies a crucial link between the physiology of intestinal environment and biological interactions between cell types." "We are interested in investigating how each newly identified cell type works in healthy and diseased conditions," adds Koh.