Many genetic (eg, ablation of CDKi75, 76, 77 or MEK178) or environmental manipulations (eg, infections or inflammation) that induce HSC proliferation and functional exhaustion are associated with increased differentiation.79, 80, 81, 82 In contrast, many of those that produce increased HSC quiescence are accompanied by reduced differentiation (eg, Neo1 downregulation83 or Atad3a deletion84). This evidence concerns the gene NEO1 and infection.