Kinase-deficient CDK6 promotes HSC self-renewal and homing. Besides its canonical role in the regulation of cell cycle progression, CDK6 also acts as a transcriptional cofactor and interacts with the transcription factors NFY-A and MAZ to regulate genes required for HSC activation and stem cell maintenance. HSCs expressing the kinase-deficient form of CDK6 have increased self-renewal and homing potential (orange arrows) compared with wild-type and CDK6 knockout HSCs. CDK6 knockout HSCs have increased quiescence and reduced self-renewal potential (purple arrows) compared with wild-type HSCs. Green dots indicate which stem cell properties of CDK6 kinase-deficient and knockout HSCs have not changed compared with wild-type cells.