Loss of Skp2 sensitizes the cells to chemotherapeutic reagents. (A) Apoptosis rate of cultured LSK cells was measured by flow cytometry after treatment with CPA, 5-FU, and DOX, (*P < .05; n = 4). (B) Apoptosis rate of freshly sorted LSK cells was measured by flow cytometry after treatment with CPA, 5-FU, and DOX (**P < .001; n = 3). (C) In vivo apoptosis rate of LSK cells from WT and Skp2^−/− mice intraperitoneally injected with 5-FU was measured by flow cytometry, 61.34% ± 5.89% in Skp2^−/− LSK cells versus 45.09% ± 2.75% in WT LSK cells (**P < .001; n = 3). (D) Validation of Skp2 shRNA knockdown efficiency. K562 were infected with lentiviral shRNAs against GFP control and Skp2, selected, and cell lysates were collected for Western blot analysis. (E) Apoptosis rate of K562 cells with GFP or Skp2 knockdown were detected by flow cytometry after treatment with CPA and 5-FU (*P < .05; n = 4). (F) The hypothetical model for the role of Skp2 in HSC functions.