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The Transcription Factor GATA2 Regulates Quiescence in Haematopoietic Stem and Progenitor Cells

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Tumor Dormancy, Quiescence, and Senescence, Volume 2

Part of the book series: Tumor Dormancy and Cellular Quiescence and Senescence ((DOQU,volume 2))

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Abstract

Control of haematopoietic stem cell (HSC) proliferation is critical in preventing bone marrow failure or haematological malignancy. Understanding the mechanisms that balance the requirement to restrain excessive HSC proliferation while allowing for production of blood cells and maintenance of the HSC pool is therefore of substantial clinical interest. Herein we discuss the nature of HSC quiescence and the role of the zinc finger transcription factor GATA2 in regulating a gene expression program which reversibly confers quiescence on HSCs and committed progenitors. We present data extending previous observations of reduced HSC and progenitor functionality in the context of enforced GATA2 expression, and begin to demonstrate the molecular mechanisms by which the GATA2 program appears to function in restraining HSC and progenitor cell proliferation. Conversely, we also show that Gata2 haploinsufficiency impacts the quiescent program of HSCs and committed progenitors, demonstrating that HSC proliferation is exquisitely responsive to either up or down-regulation of GATA2 level. Finally, we discuss the clinical manifestations of loss-of-function GATA2 mutations and high GATA2 expression in the pre-malignant myelodysplastic syndromes and myeloid leukaemia.

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Acknowledgement

This work was supported by Leukaemia Lymphoma Research, the Medical Research Council, and EuroSyStem. Funding to Neil Rodrigues was provided by National Center for Research Resources (5P20RR018757-10) and the National Institute of General Medical Sciences (8 P20 GM103414-10) from the National Institutes of Health, BD Biosciences and the Rhode Island Foundation. We acknowledge our collaborators within the laboratories of Tariq Enver and Sten Eirik Jacobsen and the Weather all Institute of Molecular Medicine, Oxford; and thank Lorenza Lazzari (Cell Factory, Milan, Italy).

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Authors and Affiliations

  1. National Institutes of Health, Center for Biomedical Research Excellence in Stem Cell Biology, Roger Williams Medical Center, Boston University of Medicine, Providence, RI, 02908, USA

    Neil P. Rodrigues

  2. Department of Dermatology, Boston University School of Medicine, Boston, MA, 02118, USA

    Neil P. Rodrigues

  3. Center for Regenerative Medicine, Boston University School of Medicine, Boston, MA, 02118, USA

    Neil P. Rodrigues

  4. Cancer Institute, University College London (UCL), Paul O’Gorman Building, 72 Huntley Street, London, WC1E 6DD, UK

    Alex J. Tipping

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  1. Neil P. Rodrigues
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Correspondence to Alex J. Tipping .

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Editors and Affiliations

  1. Department of Biological Sciences, Kean University, Room 213, Library Building, Union, New Jersey, USA

    M.A. Hayat

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Rodrigues, N.P., Tipping, A.J. (2014). The Transcription Factor GATA2 Regulates Quiescence in Haematopoietic Stem and Progenitor Cells. In: Hayat, M. (eds) Tumor Dormancy, Quiescence, and Senescence, Volume 2. Tumor Dormancy and Cellular Quiescence and Senescence, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7726-2_26

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