Transferrin receptor 1 (Tfr1) mediates the endocytosis of diferric transferrin 
in order to transport iron, and Tfr1 has been suggested to play an important 
role in hematopoiesis. To study the role of Tfr1 in hematopoiesis, we generated 
hematopoietic stem cell (HSC) specific Tfr1 knockout mice. We found that Tfr1 
conditional knockout mice reached full term but died within one week of birth. 
Further analyses revealed that Tfr1-deficient HSC had impaired development of 
all hematopoietic progenitors except thrombocytes and B lymphocytes. In 
addition, Tfr1-deficient cells had cellular iron deficiency, which blocked the 
proliferation and differentiation of hematopoietic precursor cells, attenuated 
the commitment of hematopoietic lineages, and reduced the regeneration potential 
of HSC. Notably, hemin rescued the colony-forming capacity of Tfr1-deficient 
HSC, whereas expressing a mutant Tfr1 that lacks the protein's iron-transporting 
capacity failed to rescue hematopoiesis. These findings provide direct evidence 
that Tfr1 is essential for hematopoiesis through binding diferric transferrin to 
supply iron to cells.