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Advances in the role of the aryl hydrocarbon receptor to regulate early hematopoietic development

Angelos, Mathew, G.a,b,c; Kaufman, Dan, S.d

Current Opinion in Hematology: July 2018 - Volume 25 - Issue 4 - p 273–278
doi: 10.1097/MOH.0000000000000432
HEMATOPOIESIS: Edited by Hal E. Broxmeyer

Purpose of review 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.

Recent findings 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.

Summary 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: dskaufman@ucsd.edu

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