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The Evolving Role of the Aryl Hydrocarbon Receptor (AHR) in the Normophysiology of Hematopoiesis

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Abstract

In addition to its role as a toxicological signal mediator, the Aryl Hydrocarbon Receptor (AHR) is also a transcription factor known to regulate cellular responses to oxidative stress and inflammation through transcriptional regulation of molecules involved in the signaling of nucear factor-erythroid 2-related factor-2 (Nrf2), p53 (TRP53), retinoblastoma (RB1), and NFκB. Recent research suggests that AHR activation of these signaling pathways may provide the molecular basis for understanding AHR’s evolving role in endogenous developmental functions during hematopoietic stem-cell maintenance and differentiation. Recent developments into the hematopoietic roles for AHR are reviewed, aiming to reconcile divergent findings as to the endogenous function of AHR in hematopoiesis. Potential mechanistic explanations for AHR’s involvement in hematopoietic differentiation are discussed, focusing on its known role as a cell cycle mediator and its interactions with Hypoxia-inducible transcription factor-1 alpha (HIF1-α). Understanding the physiological mechanisms of AHR activation and signaling have far reaching implications ranging from explaining the action of various toxicological agents to providing novel ways to expand stem cell populations ex vivo for use in transplant therapies.

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Acknowledgments

This work was supported by Award Numbers F32HL091620 (SL) and R21HL106397 (ETP) from the National Heart, Lung and Blood Institute of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung and Blood Institute or the National Institutes of Health.

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Authors and Affiliations

  1. Department of Chemical & Biomolecular Engineering, University of Delaware, 15 Innovation Way, Newark, DE, 19711, USA

    Stephan Lindsey & Eleftherios T. Papoutsakis

  2. Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way, Newark, DE, 19711, USA

    Stephan Lindsey & Eleftherios T. Papoutsakis

  3. Department of Biological Sciences, University of Delaware, Newark, DE, USA

    Eleftherios T. Papoutsakis

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Correspondence to Stephan Lindsey.

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Lindsey, S., Papoutsakis, E.T. The Evolving Role of the Aryl Hydrocarbon Receptor (AHR) in the Normophysiology of Hematopoiesis. Stem Cell Rev and Rep 8, 1223–1235 (2012). https://doi.org/10.1007/s12015-012-9384-5

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