[Maintenance and expansion of hematopoietic stem cell by POT1]

Expansion of stem cell numbers without reduction in their regenerative potential is crucial for therapeutic applications. However, the repeated cell divisions and aging impair stem cell function. We found that Pot1a, a component of the shelterin that protects telomeres, involves the maintenance of hematopoietic stem cell (HSC) activity during aging. Pot1a maintained the self-renewal activity of HSCs through the prevention of DNA damage responses in HSCs and suppression of the production of reactive oxygen species. Furthermore, the exogenous Pot1a expanded the HSC number and rejuvenated aged HSCs function upon ex vivo culture. Consistent with these results, treatment with exogenous human POT1 protein maintains human HSC activity in culture. Collectively, these results show that Pot1a or POT1 sustains HSC activity and can be used to expand HSC numbers ex vivo.