Intestinal stem cells articles from across Nature Portfolio

CASP5 expression is restricted to the human intestinal epithelium, and the CASP5C isoform has a key role in promoting Wnt signalling, which is required for epithelial homeostasis, through binding to dishevelled and cleavage of APC to regulate β-catenin turnover.

In fruit flies, vitamin B5 activates Myc-driven Coenzyme A biosynthesis in kidney-like cells, boosting intestinal isoprenoid production to spur stem-cell and tumor growth; human data link this pathway to worse papillary kidney cancer outcomes.

This study identifies Snora61, a snoRNA enriched in intestinal stem cells (ISCs). Snora61 knockout impairs ISC function. Snora61 binds to the Lgr5 promoter, recruiting RBMX and HMGB2 to activate Lgr5 transcription.

CBP phosphorylation keeps intestinal homeostasis by restraining CBP–p53 binding to allow sufficient versican expression. Its impairment suppresses versican, disrupting the stem cell niche to drive UC and highlighting versican as a therapeutic target.

Colon stem cells expressing the surface markers NOX1 and NPY1R can give rise to colon cancer in mice.

During cell division, a subset of intestinal stem cells (ISCs) inherits old mitochondria that increase intracellular α-ketoglutarate levels. α-Ketoglutarate facilitates remodelling of DNA methylation and boosts the ability of ISCs to regenerate the stem cell niche. Metabolite intervention with α-ketoglutarate during ageing can replace defective niche cells and enhance regeneration.

Starting from a single MLH1-knockout human colon cell, we modeled the transition of daughter cells and resultant organoids from normal epithelium to carcinoma by sequentially selecting cells with spontaneously acquired mutations. The mutations were those common in patients who have Lynch syndrome-associated colorectal cancer with high microsatellite instability, and induced insensitivity to growth factors that restrict the growth of adult stem cells.

McCarthy et al. identify distinct populations of smooth muscle cells in the intestine that support the establishment of the intestinal stem cell niche during postnatal development by supplying trophic signals to enable niche expansion.