Reprogramming mature intestinal cells: The important role of collagen was discovered for the first time

Researchers at Tokyo Medical and Dental University (TMDU) have found that collagen deposition at the site of intestinal injury activates inflammation and regeneration signals in mouse and human cells

Most cells have a fairly normal life: they are born, grow, age, and then die
.
But in the right environment, cells can again go from the old to the young
.
Now, researchers from Japan have found a physical clue that could trigger this change
in human intestinal cells.

Recently, researchers at Tokyo Medical and Dental University (TMDU) discovered that the accumulation of an extracellular substance called collagen in the injured part of the intestine stimulates cell reprogramming
.

When the intestine is injured, an inflammatory response occurs, usually related to
the regeneration of the injured tissue.
This process involves converting some mature intestinal cells back into fetal-like cells and then generating new, healthy tissue to repair the damaged area
.

Sakurako Kobayashi, lead author of the study, said: "We previously found that collagen deposition at the site of intestinal injury promoted the transformation
of gut/colonic epithelial cells into fetal-like progenitor cells in mouse wound beds.
" "However, the detailed mechanism by which this happens, and whether this process also occurs in humans, is unclear
.
"

To explore these questions, the researchers obtained collagen globules, small globules of epithelial cells grown in purified collagen
, from mouse and human intestinal cells.
They then assessed gene expression in these spheroids to elucidate the mechanisms
of inflammation-related reprogramming.

Senior author Shiro Yui explains, "The results suggest that collagen culture induces the expression
of inflammation-associated and fetal-like genes in human and mouse intestinal cells.
" "As previously reported, the YAP/TAZ-TEAD axis certainly plays a central role in inducing this unique gene expression, but this time we identified the co-transcriptional activity of Fra1 and RUNX2 in this process, which builds a fibronectin-centric gene network.
"

Importantly, representative genes activated in human collagen spheres are also highly expressed
in tissue samples from intestinal inflammatory regions of patients with ulcerative colitis.

"Overall, our results show that collagen has a significant impact
on inflammation and cellular reprogramming in both mice and humans," Kobayashi said.

Considering that some genes upregulated in collagen spheres are also overexpressed in cases such as colorectal cancer, there may be a link
between the regenerative cascade and colorectal cancer development.
Therefore, using this model to study the mechanisms of cell fate switching not only enhances our understanding of how inflammation is affected by the extracellular environment, but also how other disease processes in the gut occur
.