Reduced adhesion of aged intestinal stem cells contributes to an accelerated clonal drift.

Autor:	Hageb A; Institute of Molecular Medicine, Ulm University, Ulm, Germany., Thalheim T; Interdisciplinary Centre for Bioinformatics, University Leipzig, Leipzig, Germany., Nattamai KJ; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, USA., Möhrle B; Institute of Molecular Medicine, Ulm University, Ulm, Germany., Saçma M; Institute of Molecular Medicine, Ulm University, Ulm, Germany., Sakk V; Institute of Molecular Medicine, Ulm University, Ulm, Germany., Thielecke L; Institute for Medical Informatics and Biometry, Technische Universität Dresden, Dresden, Germany., Cornils K; Clinic of Pediatric Hematology and Oncology, Division of Pediatric Stem Cell Transplantation and Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Research Institute Children's Cancer Center Hamburg, Hamburg, Germany., Grandy C; Institute for Experimental Physics, Ulm University, Ulm, Germany., Port F; Institute for Experimental Physics, Ulm University, Ulm, Germany., Gottschalk KE; Institute for Experimental Physics, Ulm University, Ulm, Germany., Mallm JP; Division of Chromatin Networks, German Cancer Research Center (DKFZ), Heidelberg, Germany., Glauche I; Institute for Medical Informatics and Biometry, Technische Universität Dresden, Dresden, Germany., Galle J; Interdisciplinary Centre for Bioinformatics, University Leipzig, Leipzig, Germany., Mulaw MA; Central Unit Single Cell Sequencing, Medical Faculty, Ulm University, Ulm, Germany hartmut.geiger@uni-ulm.de Medhanie.Mulaw@uni-ulm.de., Geiger H; Institute of Molecular Medicine, Ulm University, Ulm, Germany hartmut.geiger@uni-ulm.de Medhanie.Mulaw@uni-ulm.de.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2022 Apr 29; Vol. 5 (8). Date of Electronic Publication: 2022 Apr 29 (Print Publication: 2022).
DOI:	10.26508/lsa.202201408
Abstrakt:	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. (© 2022 Hageb et al.)
Databáze:	MEDLINE
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