MedicalResearch.com Interview with:
Michael Sigal PhD
Clinical scientist of the Charité — Universitätsmedizin Berlin
Investigator at the Max Planck Institute for Infection Biology
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We have previously found that H. pylori can colonize gastric glands and that in colonized glands the epithelial turnover was increased. We wanted to characterize the mechanisms that control the gland turnover in the stomach.
We found that Axin2, a classic Wnt target gene, marks two different subpopulations of cells with stem cell properties, one of which is Lgr5-positive and the other one Lgr5-negative. Both populations are affected by Rspondin 3, that is produced in myofibroblasts right beneath the stem cell compartment. Rspondin is crucial for stem cell signaling and knockout of Rspondin 3 in myofibroblasts results in loss of Lgr5 and Axin2 expression. Once we increased the bioavailability of Rspondin, that now could also interact with cells outside of the stem cell compartment, we noticed that the number of Axin2 positive stem cells dramatically increased. Of interest, only Lgr5-negative cells expanded in number and proliferate more, while the Lgr5-positive cells remained silenced.
Infection with Helicobacter pylori leads to an expansion of Axin2-positive cells which is driven by increased expression of Rspondin3. Expansion of the long lived stem cell pool could be an explanation for how H. pylori infection increases the risk for gastric cancer.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: It is interesting how different cell types of the tissue communicate with each other and we show an example, including the molecular details, how this communication is organized and how it dynamically adapts to infection.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: I think it will be very important to address the question of how and why different subpopulations of stem cells can have differential responses to the same stimulus. What is the molecular basis for this. And also, what are the consequences?
No financial conflicts of interest.
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Michael Sigal, Catriona Y. Logan, Marta Kapalczynska, Hans-Joachim Mollenkopf, Hilmar Berger, Bertram Wiedenmann, Roeland Nusse, Manuel R. Amieva, Thomas F. Meyer. Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis. Nature, 2017; DOI: 10.1038/nature23642
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