Suppression of elevated Cdc42 activity promotes the regenerative potential of aged intestinal stem cells.

Autor:	Nalapareddy K; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA., Hassan A; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA., Sampson LL; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA., Zheng Y; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA., Geiger H; Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2021 Mar 26; Vol. 24 (4), pp. 102362. Date of Electronic Publication: 2021 Mar 26 (Print Publication: 2021).
DOI:	10.1016/j.isci.2021.102362
Abstrakt:	Homeostasis in the intestinal epithelium is maintained by Lgr5-positive intestinal stem cells (ISCs) located at the base of the crypt. The function of ISCs is reduced upon aging which leads to a decline of regeneration of the intestinal epithelium. We report that aged intestinal crypts present with an elevated activity of the small RhoGTPase Cdc42. Elevation of Cdc42 activity in young animals by genetic means causes premature ISC aging, whereas pharmacological suppression of elevated Cdc42 activity restores organoid formation potential in vitro . Consistent with a critical role of elevated Cdc42 activity in aged ISCs for a reduced regenerative capacity of aged ISCs, suppression of Cdc42 activity in vivo improves crypt regeneration in aged mice. Thus, pharmacological reduction of Cdc42 activity can improve the regeneration of aged intestinal epithelium. Competing Interests: H.G and Y.Z are inventors on patent US20150297563A1, Rejuvenation of precursor cells, which comprises, among others, methods of rejuvenating intestinal tissue via inhibition of GTPases. (© 2021 The Authors.)
Databáze:	MEDLINE
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