Reduced adhesion of aged intestinal stem cells contributes to an accelerated clonal drift
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Reduced adhesion of aged intestinal stem cells contributes to an accelerated clonal drift. / Hageb, Ali; Thalheim, Torsten; Nattamai, Kalpana J; Möhrle, Bettina; Saçma, Mehmet; Sakk, Vadim; Thielecke, Lars; Kerstin, Cornils; Grandy, Carolin; Port, Fabian; Gottschalk, Kay-E; Mallm, Jan-Philipp; Glauche, Ingmar; Galle, Jörg; Mulaw, Medhanie A; Geiger, Hartmut.
in: LIFE SCI ALLIANCE, Jahrgang 5, Nr. 8, e202201408, 08.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Reduced adhesion of aged intestinal stem cells contributes to an accelerated clonal drift
AU - Hageb, Ali
AU - Thalheim, Torsten
AU - Nattamai, Kalpana J
AU - Möhrle, Bettina
AU - Saçma, Mehmet
AU - Sakk, Vadim
AU - Thielecke, Lars
AU - Kerstin, Cornils
AU - Grandy, Carolin
AU - Port, Fabian
AU - Gottschalk, Kay-E
AU - Mallm, Jan-Philipp
AU - Glauche, Ingmar
AU - Galle, Jörg
AU - Mulaw, Medhanie A
AU - Geiger, Hartmut
N1 - © 2022 Hageb et al.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - Animals
KW - Cells, Cultured
KW - Ileum
KW - Intestinal Mucosa/metabolism
KW - Intestines
KW - Mice
KW - Stem Cells/metabolism
U2 - 10.26508/lsa.202201408
DO - 10.26508/lsa.202201408
M3 - SCORING: Journal article
C2 - 35487692
VL - 5
JO - LIFE SCI ALLIANCE
JF - LIFE SCI ALLIANCE
SN - 2575-1077
IS - 8
M1 - e202201408
ER -