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The real ‘reserve’ intestinal stem cells
Murata K, Jadhav U, Madha S, et al. Ascl2-Dependent Cell Dedifferentiation Drives Regeneration of Ablated Intestinal Stem Cells. Cell Stem Cell 2020; 263,: 377-390
In the intestinal crypt, when stem cells are damaged, it was previously thought that a reserve group of stem cells in the +4 position stepped in to replace them. Since then several papers have shown that various postmitotic cell types may be capable of dedifferentiating and replenishing damaged stem cells. This paper definitively shows that a group of differentiated progenitors are responsible for restoring the stem cell compartment. Murata et al used a mouse model in which Lgr5 stem cells were fluorescently labelled and used radiation to ablate stem cells. If either secretory or enterocyte cells were ablated using Notch signalling pathway knockout models, the other cell type dedifferentiated and allowed Lgr5+ stem cell recovery. Ascl2 is a Wnt-responsive transcription factor known to regulate stem cells. Ascl2 knockout mice were healthy in homoeostatic conditions, but after irradiation or diphtheria toxin damage, intestinal crypt cell proliferation was compromised and the mice did not survive. Ascl2 cell labelling showed that cells expressed Ascl2 days before Lgr5 expression, and it was in the upper crypt where this re-expression occurred. Flow cytometry and RNA sequencing revealed these cells to have markers of goblet cells and enterocytes. Ascl2 target genes were found to include interleukin receptor 11 gene, IL11ra1, recognised as a regulator in stem cell renewal. The authors concluded that differentiated secretory and absorptive cell progenitors in the upper crypt dedifferentiate after stem cell damage via Ascl2 re-expression and replace intestinal stem cells.
Enteric nervous system: the protagonist in barrier immune responses?
Jarret A, Jackson R, Duizer C, et al. Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity Cell 2020; 180(1): 50-63.e12
The interactions between the nervous and immune systems have been shown to maintain the …
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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