Extracellular nucleotides counteract a 5-fold decrease of cytokine concentrations to stimulate the optimal growth of CD34⁺ HSCs and synergize with other cytokines to induce colony formation of Lin^-CD34^- HSCs. CD34⁺ cells were plated in serum-free medium with suboptimal concentrations of GM-CSF/EPO and SCF/EPO combinations with and without a fixed dose of UTP (10 μM). The results (A-C) represent the mean ± SEM of 4 different experiments. (D-F) Cells (1 × 10⁴ Lin^-CD34^-) were plated in methylcellulose under serum-depleted conditions and stimulated with optimal concentrations of ATP or UTP alone, GM-CSF/IL-3/SCF/EPO (together referred to as CSFs), and the combination of the cytokine cocktail plus UTP or ATP. The results represent the mean ± SEM of 3 different experiments. The addition of ATP or UTP makes HSCs significantly more responsive to additional growth factors. ^*P < .05.