Role of p53 in HSC exhaustion. (A) Number of colonies arising from 10⁴ Lin⁻ Sca-1⁺c-Kit⁺ CD34^low/− (upper panel) or Lin⁻ Sca-1⁺ c-Kit⁺CD34^high/+ (lower panel) cells passaged every 10 days in methylcellulose semisolid medium containing KL, IL-3, and Epo. Results are mean (standard deviation) from three experiments. (B) BMCs were cocultured on irradiated stromal layers and clonogenic activity was measured every 2 weeks in the presence of KL. Results are mean (standard deviation) from two independent experiments (3 mice per experiment). (C) CFU-S and pre–CFU-S were counted on day 12 after BMC transplantation. Mean (standard deviation) from six mice. * Only microscopic colonies were present. Black and shadowed bars represent results from p53+/+ and p53−/− cells, respectively.