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Cell Stem Cell. 2012 May 4;10(5):520-30. doi: 10.1016/j.stem.2012.04.007.

Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation.

Author information

1
Department of Dermatology and Allergic Diseases, University of Ulm, 89091 Ulm, Germany.

Abstract

The decline in hematopoietic function seen during aging involves a progressive reduction in the immune response and an increased incidence of myeloid malignancy, and has been linked to aging of hematopoietic stem cells (HSCs). The molecular mechanisms underlying HSC aging remain unclear. Here we demonstrate that elevated activity of the small RhoGTPase Cdc42 in aged HSCs is causally linked to HSC aging and correlates with a loss of polarity in aged HSCs. Pharmacological inhibition of Cdc42 activity functionally rejuvenates aged HSCs, increases the percentage of polarized cells in an aged HSC population, and restores the level and spatial distribution of histone H4 lysine 16 acetylation to a status similar to that seen in young HSCs. Our data therefore suggest a mechanistic role for Cdc42 activity in HSC biology and epigenetic regulation, and identify Cdc42 activity as a pharmacological target for ameliorating stem cell aging.

PMID:
22560076
PMCID:
PMC3348626
DOI:
10.1016/j.stem.2012.04.007
[Indexed for MEDLINE]
Free PMC Article

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