Suppression of Elevated Cdc42 Activity Promotes the Regenerative Potential of Aged Intestinal Stem Cells

Overview

Journal iScience

Publisher Cell Press

Date 2021 Apr 19

PMID 33870147

Citations 12

Authors

Kodandaramireddy Nalapareddy

Aishlin Hassan

Leesa L Sampson

Yi Zheng

Hartmut Geiger

Affiliations

Soon will be listed here.

Abstract

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 . Consistent with a critical role of elevated Cdc42 activity in aged ISCs for a reduced regenerative capacity of aged ISCs, suppression of Cdc42 activity improves crypt regeneration in aged mice. Thus, pharmacological reduction of Cdc42 activity can improve the regeneration of aged intestinal epithelium.

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