SHIP deficiency alters the function of BM niche cells. (A) ALP-positive cells from cultures of SHIP^−/− and WT osteoblasts showing altered phosphatase kinetics at 1, 15, and 30 minutes. (B) Representative FACS plots illustrating gating strategy for ALP-positive cells based on ALP-negative BM controls and showing ALP kinetics at increasing time points. (C) Frequency of Lin⁻cKit⁺Flk2⁻ (KFL) stem/progenitor cells among Lin-depleted BM cells (HPCs) cultured alone (□), or with SHIP^−/− (■) or WT () stromal cells in each cell division after 36 hours. (D) Representative histograms showing decreased proliferation of CFSE⁺ KFL cells cultured with SHIP^−/− stromal cells (top) compared with those cultured with WT stromal cells (bottom). Significance was established using the unpaired Student t test (*P < .05; **P < .005; ***P < .001). ■ represent SHIP^−/− osteoblasts (A); , WT osteoblasts (A); □, WT HPCs alone (C); ■, HPCs cultured with SHIP^−/− stroma (C); , HPCs cultured with WT stroma (C).