While our functional experiments demonstrate the cell‐extrinsic role of HO‐1 in regulation of HSC exhaustion, the question remains whether this cell‐extrinsic role is mediated by local HSC niche or by systemic factors, e.g., linked to iron deficiency and microcytic anemia in HO‐1−/− mice. This evidence concerns the gene HMOX1 and Iron deficiency anemia.