We summarize current advances to define the role the aryl hydrocarbon receptor (AHR) plays in mammalian hematopoiesis. We emphasize approaches to modulate AHR throughout human hematopoietic development in vitro to support the production of clinically relevant blood products suitable for patient care.
Initial data demonstrate that both pharmacologic AHR inhibition and genetic deletion from human pluripotent stem cells provide useful strategies to enhance the yield of hematopoietic stem and progenitor cells. AHR hyperactivation following the induction of CD34+ megakaryocyte–erythroid progenitors skews developed toward erythroid lineages, whereas AHR inhibition supports platelet production. At the level of lymphoid specification, AHR inhibition enhances the proliferation and differentiation of functional human natural killer cells, whereas hyperactivation leads to production of Group 3 innate lymphoid cells and provides a novel platform for studying human innate lymphoid cell development.
Modulation of AHR in human hematopoietic cells in vitro is a promising tool to mediate development of terminal hematopoietic cell populations with significant clinical implications to generate cells suitable for antitumor immunotherapy and bone marrow transplantation.
aDivision of Hematology, Oncology, and Transplantation, Department of Medicine
bStem Cell Institute
cMedical Scientist Training Program, University of Minnesota, Minneapolis, Minnesota
dDivision of Regenerative Medicine, Department of Medicine, University of California-San Diego, La Jolla, California, USA
Correspondence to Dan S. Kaufman, MD, PhD, 9500 Gilman Drive, MC 0695, La Jolla, CA, 92093–0695, USA. Tel: +858 822 1777; e-mail: firstname.lastname@example.org