On how Rac controls hematopoietic stem cell activity

Rac GTPases form part of the family of Rho small GTPases. Rac GTPases, like other Rho family GTPases, are key molecular switches controlling the transduction of external signals to cytoplasmic and nuclear effectors. The development of genetic and pharmacological tools has allowed a more precise definition of the specific roles of Rac GTPases in hematopoietic stem cells (HSCs). Our current knowledge has enabled dissection of their specific and redundant roles. Rac GTPases are now known to be crucial in the response of HSCs to the hematopoietic microenvironment cues. This review will briefly summarize the known HSC functions that are regulated by Rac GTPases, focusing on adhesion, migration, retention, proliferation, and survival, and how Rac relates to the physiological functions of HSC. The development of small molecule inhibitors with the ability to interfere with Rac GTPase activation offers new therapeutic strategies to manipulate the function of HSC in vivo and ex vivo.