Drosophila Intestinal Stem Cell RNA Sequencing

Intestinal epithelium regeneration and homeostasis must be tightly regulated. Alteration of epithelial homeostasis is a major contributing factor to diseases such as colorectal cancer and inflammatory bowel diseases. Many pathways involved in epithelial regeneration have been identified, but more regulators remain undiscovered. Metabolic signals have emerged as overlooked regulators of intestinal epithelium homeostasis. Using the model organism Drosophila melanogaster, we found that ether lipid metabolism is required to maintain intestinal epithelial homeostasis. Its dysregulation in intestinal progenitors causes the activation of the unfolded protein response of the endoplasmic reticulum (UPR) that upregulates PDIA3/ERp60, which increases progenitor cells, affecting epithelial barrier function in males. Considering that human PDIA3 is linked to cancer and fibrosis, this study identified ether lipids-PDIA3/ERp60 as a key regulator of intestinal progenitor homeostasis in health that, if altered, cause pathological conditions in the intestinal epithelium.