/news/new-insights-how-gut-cells-respond-bacterial-toxins
Researchers from the Organoid group at the Hubrecht Institute have found that specific gut cells, BEST4/CA7+ cells, regulate electrolyte and water balance in response to bacterial toxins that cause diarrhea. Their findings, published in Cell Stem Cell, show that these cells greatly increase in number when exposed to the cytokine interferon-γ (IFNγ), presenting a promising target for therapeutic strategies.
In the gut, a variety of cell types collaborate to keep a balance of electrolyte and water. Bacterial infections can disrupt this balance, leading to diarrhea. Yet, it was unclear which cells were mainly affected by these toxins. “In this study, we looked at the recently identified BEST4/CA7+ cells, a specific type of cell in the intestinal lining that highly expresses CFTR, an important ion channel for electrolyte balance”, says Daisong Wang, lead author of the study.
Understanding how BEST4/CA7+ cells develop
While researchers previously identified the presence of BEST4/CA7+ cells, their development and function are not well understood due to the lack of study models. Wang and his colleagues overcame this by creating human intestinal organoids, mini organ-like structures cultured in a dish. They used these organoids to experimentally assess the response of BEST4/CA7+ cells to various specific signals. “Using cell-type specific reporter organoids and CRISPR-mediated genetic modifications, we found that the Notch signaling pathway and a master regulator named SPIB are crucial for these cells’ development”, Wang notes.
BEST4/CA7+ cells: key targets in diarrhea
The team previously observed swelling of the organoid when the ion channel CFTR was activated. “However, we saw that organoids lacking BEST4/CA7+ cells did not show this swelling, confirming the vital role of these cells in controlling fluid balance”, Wang explains. This shows that BEST4/CA7+ cells are key targets in diarrhea.