Researchers at Brigham and Women's Hospital, in collaboration with Boston Children's Hospital, have utilized a cutting-edge technique called MERFISH (multiplexed-error robust-fluorescence in situ hybridization) to analyze the cellular landscape of the mouse intestine, both in healthy and inflamed states.
The study, which examined 940 genes in 1.35 million intestinal cells identified distinct cell populations associated with healthy and inflamed conditions, and mapped their spatial organization within the tissue. One key finding was the identification of fibroblasts that, when in a distressed state, can transform into inflammation-associated fibroblasts (IAFs). These IAFs play a crucial role in remodeling the extracellular matrix, recruiting immune cells, and producing inflammatory cytokines.
The researchers generated a comprehensive spatial atlas of the mouse colon, providing valuable insights into the cellular interactions and communication within the gut during inflammation. This work has the potential to assist in the development of therapeutic treatments for chronic inflammatory diseases, as IAFs have been observed in a variety of conditions, including cancers and autoimmune disorders.
"Our team wanted to better understand how cells are organized within the gut, and how inflammation can impact cellular interactions and communication at the tissue scale," said Roni Nowarski, senior author of the study published in Cell. "This work is particularly exciting and has given us a better understanding of the tissue context of cellular responses during inflammation, which we hope will help us design better therapeutics to fight serious chronic inflammatory diseases.”
While some key questions remain, such as the specific diversity of IAF populations and their precise tissue locations, this study provides a valuable spatial atlas that can inform future research and therapeutic strategies targeting intestinal inflammation.