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An in vitro model of colitis and a new colitis-associated stem cell population
Wang Y, Chiang IL, Ohara TE, et al. Long-term culture captures injury-repair cycles of colonic stem cells. Cell 2019; 179:1144–59.
A stem cell population that mediates regeneration in colitis is unidentified. This is in part due to the challenge of an in vitro epithelial system with the continuous process of damage and repair. The authors used a chemical induced model of colitis (dextran sulphate sodium (DSS)) to show that crypts became atrophic during injury, with reduced expression of Lgr5 and Hopx. Subsequently hypertrophic crypts appeared adjacent to ulcers, and Hopx expression re-emerged in these crypts. An inducible Hopx-labelled mouse model showed that the Hopx positive cells also expressed the foetal-like marker Tacstd2. The Hopx cells could be lineage traced and gave rise to multiple differentiated cell lines. Sorted Hopx+ cells could form spheroids in culture. Ablation of Hopx cells after DSS injury led to apoptosis of the hypertrophic crypts and shorter colons. An in vitro epithelial monolayer was created by dissociating colonic spheroids into single cells and plating onto Transwell membranes submerged in medium for 7 days, before exposing them to an air–liquid interface (ALI). Hopx, but not Lgr5, labelled cells were expressed at the start of regeneration, which gave rise to the monolayer. Re-submerging and then re-exposing the monolayer to the ALI recapitulated the injury-regeneration cycle. Hopx was temporarily lost then re-emerged. Cellular stress was mediated by low oxygen tension, as it induced HIF1-mediated signalling. The authors give evidence that Hopx+ cells function as regenerative stem cells in colitis and oxygen tension acts as a switch between injury and regeneration.
Targeting gut bacteria to treat alcoholic hepatitis
Duan Y, Llorente C, Lang S, et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature 2019;575:505–11. doi:10.1038/s41586-019-1742-x.
Alcoholic hepatitis (AH) continues to have a high mortality with limited treatment options available. In this article …
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; internally peer reviewed.
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