Life science alliance · 2022
Reduced adhesion of aged intestinal stem cells contributes to an accelerated clonal drift.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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История · было → стало
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Hageb Ali, Thalheim Torsten, Nattamai Kalpana J, Möhrle Bettina, Saçma Mehmet, Sakk Vadim, Thielecke Lars, Cornils Kerstin, Grandy Carolin, Port Fabian, Gottschalk Kay-E, Mallm Jan-Philipp, Glauche Ingmar, Galle Jörg, Mulaw Medhanie A, Geiger Hartmut
Аннотация
Upon aging, the function of the intestinal epithelium declines with a concomitant increase in aging-related diseases. ISCs play an important role in this process. It is known that ISC clonal dynamics follow a neutral drift model. However, it is not clear whether the drift model is still valid in aged ISCs. Tracking of clonal dynamics by clonal tracing revealed that aged crypts drift into monoclonality substantially faster than young ones. However, ISC tracing experiments, in vivo and ex vivo, implied a similar clonal expansion ability of both young and aged ISCs. Single-cell RNA sequencing for 1,920 high Lgr5 ISCs from young and aged mice revealed increased heterogeneity among subgroups of aged ISCs. Genes associated with cell adhesion were down-regulated in aged ISCs. ISCs of aged mice indeed show weaker adhesion to the matrix. Simulations applying a single cell-based model of the small intestinal crypt demonstrated an accelerated clonal drift at reduced adhesion strength, implying a central role for reduced adhesion for affecting clonal dynamics upon aging.