An author says the paper, published in Science on October 15, finds signaling rhythms matter to intestinal cell balance.
An author announced the paper's publication in Science on October 15, saying it finds that signaling rhythms matter to how the intestine maintains the right balance of cell types. The author also credited three shared first authors.
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Researchers at the Hubrecht Institute and collaborating labs found that intestinal cells can respond not just to the strength of a signal, but also to its tempo. In a study published in Science on Oct. 15, they report that oscillations in Hes1, a protein controlled by the Notch signaling pathway, help determine which cell types develop in the small intestine.
The team used a fluorescent Hes1 reporter in mice to watch the protein's activity in living intestinal tissue, then examined the pattern in three-dimensional intestinal organoids. Hes1 levels rose and fell roughly every 75 to 200 minutes. Cells near the base of intestinal crypts, where stem cells are concentrated, had faster oscillations of about 90 minutes. Cells farther along the crypt-villus axis oscillated more slowly, with periods near 170 minutes.
That pattern suggested timing might help cells interpret a familiar signal. Notch activity is already known to influence whether intestinal cells remain stem-like or differentiate into absorptive and secretory types. The new results indicate that the pathway can carry additional information through frequency, rather than signal level alone.
To test that idea, the researchers built a microfluidic system that delivered precisely timed pulses of a Notch inhibitor to organoids. Imposing 90-minute Hes1 oscillations increased the number of stem and progenitor cells as well as Paneth cells. A 130-minute rhythm instead promoted the broader secretory lineage. The paper reports that these changes were not caused by differences in overall Notch signal levels.
The finding offers a mechanism for how the intestinal lining maintains a useful mix of specialized cells while renewing itself every five to seven days, as the Hubrecht Institute explains. The authors say similar timing-based control may matter in other tissues, but broader implications for inflammation, regeneration or cancer remain questions for future research. The experiments here were conducted in mouse tissue and lab-grown organoids, not in patients.
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@SonnenKatharina🎉 Our paper is out today in @ScienceMagazine! How does the intestine maintain the right balance of cell types? We find that signalling rhythms matter! So proud of our three shared first authors, Sonja Weterings, @HiromuneEto & @jddeleede! 🔗 https://www.science.org/doi/10.1126/science.adt1928@SonnenKatharina🎉 Our paper is out today in @ScienceMagazine! How does the intestine maintain the right balance of cell types? We find that signalling rhythms matter! So proud of our three shared first authors, Sonja Weterings, @HiromuneEto & @jddeleede! 🔗 https://www.science.org/doi/10.1126/science.adt1928@SonnenKatharina🎉 Our paper is out today in @ScienceMagazine! How does the intestine maintain the right balance of cell types? We find that signalling rhythms matter! So proud of our three shared first authors, Sonja Weterings, @HiromuneEto & @jddeleede! 🔗 https://www.science.org/doi/10.1126/science.adt1928@SonnenKatharina🎉 Our paper is out today in @ScienceMagazine! How does the intestine maintain the right balance of cell types? We find that signalling rhythms matter! So proud of our three shared first authors, Sonja Weterings, @HiromuneEto & @jddeleede! 🔗 https://www.science.org/doi/10.1126/science.adt1928
