Intestinal Epithelial Cells Adapt to Chronic Inflammation through Partial Genetic Reprogramming.

Area of Science:

• Cell biology
• Gastroenterology
• Oncology

Background:

• Reactive oxygen species (ROS) are implicated as key drivers in inflammatory bowel diseases (IBD).
• Intestinal stem cells may develop adaptive strategies to counteract ROS-induced damage.
• This adaptation could enhance tolerance to oncogenic insults, promoting neoplastic transformation.

Purpose of the Study:

• To investigate adaptive strategies of intestinal stem cells to chronic oxidative stress.
• To explore the link between ROS adaptation, IBD progression, and colorectal cancer initiation.
• To identify genetic reprogramming associated with oxidative stress in intestinal epithelial cells.

Main Methods:

• Immortalized human colonic epithelial cells were exposed to chronic inflammation mimics or chemical peroxide.
• Gene set enrichment analysis was used to identify adaptive programs.
• Database analysis and murine models were employed to assess biological relevance in IBD and colorectal cancer.

Main Results:

• Cells adapted to oxidative stress through partial genetic reprogramming.
• This reprogramming program is active in Crohn's disease and ulcerative colitis patient mucosa and progresses with disease.
• The adaptive program was confirmed in intestinal precursor cells during murine colorectal cancer development.

Conclusions:

• Cellular adaptation to oxidative stress in IBD involves genetic reprogramming.
• This adaptive process may contribute to IBD progression and colorectal cancer initiation.
• Understanding this mechanism offers insights into IBD pathogenesis and cancer development.