Hypoxia Increases the Proliferation of Control BFU-E Colonies but Decreases that of Colonies With the c.[12C>G; 380G>C] Mutation in EGLN1. BFU-Es were grown in 3,000 mU/mL EPO; and all images were acquired at 40× magnification (scale bars, 1 mm). (a,b) Representative colonies from a control (wild-type) subject and (c,d) a Tibetan subject homozygous for the c.[12C>G; 380G>C] mutation. Note the larger colony sizes for the control BFU-E colonies under hypoxia (5% O2) (b) relative to ambient oxygen tension (a). BFU-Es with the c.[12C>G; 380G>C] mutation exhibit smaller colony sizes under normoxia (c) in comparison to control cells (a), and the colonies are paler than the controls, reflecting the decreased hemoglobinization with the c.[12C>G; 380G>C] erythroid progenitors in comparison to the controls. (d) The decrease in colony size and hemoglobinization for Tibetan BFU-Es with the c.[12C>G; 380G>C] mutation is even more pronounced under 5% O2 (in comparison with b).Reprinted with permission from Nature Publishing Group (Lorenzo FR et al. Nat Genet. 2014;46:951-956.)