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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Ali Hageb - , Universität Ulm (Autor:in)
  • Torsten Thalheim - , Universität Leipzig (Autor:in)
  • Kalpana J Nattamai - , Cincinnati Children's Hospital Medical Center (Autor:in)
  • Bettina Möhrle - , Universität Ulm (Autor:in)
  • Mehmet Saçma - , Universität Ulm (Autor:in)
  • Vadim Sakk - , Universität Ulm (Autor:in)
  • Lars Thielecke - , Institut für Medizinische Informatik und Biometrie (Autor:in)
  • Kerstin Cornils - , Universität Hamburg (Autor:in)
  • Carolin Grandy - , Universität Ulm (Autor:in)
  • Fabian Port - , Universität Ulm (Autor:in)
  • Kay-E Gottschalk - , Universität Ulm (Autor:in)
  • Jan-Philipp Mallm - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Ingmar Glauche - , Institut für Medizinische Informatik und Biometrie (Autor:in)
  • Jörg Galle - , Universität Leipzig (Autor:in)
  • Medhanie A Mulaw - , Universität Ulm (Autor:in)
  • Hartmut Geiger - , Universität Ulm (Autor:in)

Abstract

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.

Details

OriginalspracheEnglisch
Aufsatznummere202201408
Seitenumfang16
FachzeitschriftLife science alliance
Jahrgang5
Ausgabenummer8
PublikationsstatusVeröffentlicht - Aug. 2022
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC9057243
Scopus 85129163127
unpaywall 10.26508/lsa.202201408
ORCID /0000-0002-2524-1199/work/142251495
ORCID /0000-0002-5726-4491/work/153109651

Schlagworte

Schlagwörter

  • Animals, Cells, Cultured, Ileum, Intestinal Mucosa/metabolism, Intestines, Mice, Stem Cells/metabolism