Expression of activated Kras compensates for loss of Ptpn11 in HSCs and progenitors. (A) Primary myeloid progenitors from embryonic day 14.5 Ptpn11^flox/flox fetal livers were transduced with the indicated retroviruses, and FACS-purified GFP⁺ cells were cultured in methylcellulose medium containing granulocyte-macrophage colony-stimulating factor. GFP virus served as a negative control. MIG-Cre vectors were designed to coexpress the hygromycin resistance gene, WT Ptpn11, WT Kras, or activated Kras^G12D. Results are shown as mean ± SEM of 3 independent experiments. *P < .05, Student t test. **P < .01, Student t test. (B) Effect of Ptpn11 loss in Ptpn11^flox/flox fetal liver cells with or without an activated Kras^LSL-G12D allele. Cells of the indicated genotype were transduced with GFP virus control or with MIG-Cre virus coexpressing exogenous Ptpn11 or the hygromycin resistance gene. Results are shown as mean ± SEM of 3 independent experiments. *P < .05, Student t test. (C) SLAM-HSCs from control (n = 2) and Mx1-Cre; Kras^LSL-G12D; Ptpn11^flox/flox (n = 4) mice were purified by FACS and deposited into 60-well plates (1 cell/well), and proliferation of each clone was evaluated microscopically over 3 days. The average percentages (± SEM) of surviving clones are shown at the top of each panel. Representative data from these experiments with similar results are shown.