Journal
CURRENT OPINION IN HEMATOLOGY
Volume 25, Issue 4, Pages 273-278Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOH.0000000000000432
Keywords
aryl hydrocarbon receptor; hematopoietic stem cells; innate immune cells; natural killer cells
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Funding
- National Institutes of Health: National Cancer Institute [R01 CA203348, U01 CA217885]
- National Institutes of Health: National Institute of Diabetes and Digestive and Kidney Diseases [F30 DK107071]
- National Institutes of Health: California Institute for Regenerative Medicine
- Fate Therapeutics
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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.
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