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

Kodandaramireddy Nalapareddy; Aishlin Hassan; Leesa L Sampson; Yi Zheng; Hartmut Geiger

doi:10.1016/j.isci.2021.102362

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

iScience. 2021 Mar 26;24(4):102362. doi: 10.1016/j.isci.2021.102362. eCollection 2021 Apr 23.

Authors

Kodandaramireddy Nalapareddy¹, Aishlin Hassan¹, Leesa L Sampson¹, Yi Zheng¹, Hartmut Geiger¹

Affiliation

¹ Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.

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 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.

Keywords: Cell Biology; Functional Aspects of Cell Biology; Stem Cells Research.

Abstract

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