Mechanism of action of HOXB4 on the hematopoietic differentiation of embryonic stem cells

Pluripotent stem cells can be differentiated into hematopoietic lineages in vitro and hold promise for the future treatment of hematological disease. Differentiation strategies involving defined factors in serum-free conditions have been successful in producing hematopoietic progenitors and some mature cell types from mouse and human embryonic stem cells and induced pluripotent cells. However, these precisely defined protocols are relatively inefficient and have not been used successfully to produce hematopoietic stem cells capable of multilineage long-term reconstitution of the hematopoietic system. More complex differentiation induction strategies including coculture with stromal cells derived from sites of hematopoietic activity in vivo and enforced expression of reprogramming transcription factors, such as HOXB4, have been required to increase the efficiency of the differentiation procedure and to produce these most potent hematopoietic stem cells. We review the studies that have used HOXB4 to improve hematopoietic differentiation from pluripotent cells focusing on studies that have provided some insight into its mechanism of action. A better understanding of the molecular pathways involved in the action of HOXB4 might lead to more defined culture systems and safer protocols for clinical translation.