High-Resolution Map Tracks Cellular Changes During Inflammation

Cells within the intestines fulfill diverse functions, including nutrient absorption, sensing, and regulating homeostasis. Gut inflammation is a characteristic that sets certain chronic disorders apart. It disrupts intestinal cells and can result in gut remodeling and the introduction of new immune cells.

Researchers at Boston Children's Hospital and Brigham and Women's Hospital, founding members of the Mass General Brigham healthcare system, collaborated to analyze 940 genes in 1.35 million intestinal cells in a mouse model of colitis using a novel technique called MERFISH (multiplexed-error robust-fluorescence in situ hybridization). This analysis was made to gain a better understanding of the types of cells and their positioning within the intestines.

They recognized cell populations linked to both healthy and inflammatory conditions, charted the spatial neighborhoods of these populations, and followed their development throughout inflammation. Fibroblasts are a noteworthy cell type that can trigger the production of inflammatory cytokines, recruit immune cells, and remodel extracellular matrixes when they are distressed. This is known as inflammation associated fibroblasts (IAFs).

The precise tissue locations of IAF populations, their unique diversity, and how they arise during inflammation are not answered yet. However, the scientists were able to create a distinct spatial atlas of a mouse colon during intestinal inflammation as well as in a healthy state, which may help with therapeutic interventions for long-term inflammatory illnesses.

Understanding the function and mechanisms of IAFs may aid in the development of treatments for the various diseases that have been linked to IAFs in the past, such as autoimmune diseases and cancers.

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. 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.”

Roni Nowarski Ph.D., Study Senior Author, Department of Immunology, Harvard Medical School

Source:
Journal reference:

Cadinu, P., et al. (2024) Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling. Celldoi.org/10.1101/2023.05.08.539701.

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