Hypoxia impacts small intestinal organoid stemness and differentiation

Comprised of several cell types functioning differently, the small intestinal epithelial cells perform their functions and synergistically maintain homeostasis in the first part of the mammalian intestine. Due to the uneven distribution of the vessel, the oxygen level exhibits a gradient decreasing pattern in the normal intestine and becomes aberrant in some intestinal diseases. In this work, we find certain levels of hypoxia simulated by cobaltous chloride (CoCl2) caused an increase in the secretive cell types and a decrease in the absorptive cell types in vitro cultured mouse small intestinal organoids. Importantly, the intestinal stem cell amount is impacted which leads to attenuated epithelial regeneration. Our study highlights the cell-type-specific alterations under the hypoxia insult, which gives possible therapeutic hints for hypoxia-relevant gastrointestinal diseases.