The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function by effects on cell cycle
Abstract
Evidence suggests the transcription factor GATA-2 is a critical regulator of murine hematopoietic stem cells. Here, we explore the relation between GATA-2 and cell proliferation and show that inducing GATA-2 increases quiescence (G0 residency) of murine and human hematopoietic cells. In human cord blood, quiescent fractions (CD34+CD38−HoechstloPyronin Ylo) express more GATA-2 than cycling counterparts. Enforcing GATA-2 expression increased quiescence of cord blood cells, reducing proliferation and performance in long-term culture-initiating cell and colony-forming cell (CFC) assays. Gene expression analysis places GATA-2 upstream of the quiescence regulator MEF, but enforcing MEF expression does not prevent GATA-2–conferred quiescence, suggesting additional regulators are involved. Although known quiescence regulators p21CIP1 and p27KIP1 do not appear to be responsible, enforcing GATA-2 reduced expression of regulators of cell cycle such as CCND3, CDK4, and CDK6. Enforcing GATA-2 inhibited human hematopoiesis in vivo: cells with highest exogenous expression (GATA-2hi) failed to contribute to hematopoiesis in nonobese diabetic–severe combined immunodeficient (NOD-SCID) mice, whereas GATA-2lo cells contributed with delayed kinetics and low efficiency, with reduced expression of Ki-67. Thus, GATA-2 activity inhibits cell cycle in vitro and in vivo, highlighting GATA-2 as a molecular entry point into the transcriptional program regulating quiescence in human hematopoietic stem and progenitor cells.
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“Reports on the role of GATA-2 in eosinophil differentiation and function have shown that it can have positive, as well as negative regulatory functions. 8 -14”
From RhoH is a negative regulator of eosinophilopoiesis (2016) · cites this paper as [10]
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Self-citationRadiation-induced cell cycle arrest compromised by p21 deficiency
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Wilson, N. K., Foster, S. D., Wang, X., Knezevic, K., Schütte, J., Kaimakis, P., Chilarska, P. M., Kinston, S., Ouwehand, W. H., Dzierzak, E., et al. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.07.016 · Cited by 728
Inferring rules of lineage commitment in haematopoiesis
Pina, C., Fugazza, C., Tipping, A. J., Brown, J., Soneji, S., Teles, J., Peterson, C., & Enver, T. (2012) · Nature Cell Biology · doi:10.1038/ncb2442 · Cited by 162
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RhoH is a negative regulator of eosinophilopoiesis
Stoeckle, C., Geering, B., Yousefi, S., Rožman, S., Andina, N., Benarafa, C., & Simon, H.-U. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2016.73 · Cited by 24
Metadata
- Authors
- Tipping, A. J., Pina, C., Castor, A., Hong, D., Rodrigues, N. P., Lazzari, L., May, G. E., Jacobsen, S. E. W., & Enver, T.
- Affiliations
- Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;
- Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden;
- Cell Factory, Center for Transfusion Medicine, Cellular Therapy and Cryobiology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy; and
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2009-03-19
- Volume
- 113
- Issue
- 12
- Pages
- 2661-2672
- ISSN
- 0006-4971
- 1528-0020
- Cited by
- 116
- References
- 47
- Language
- en
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- Tipping, A. J., Pina, C., Castor, A., Hong, D., Rodrigues, N. P., Lazzari, L., May, G. E., Jacobsen, S. E. W., & Enver, T. (2009). High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function by effects on cell cycle. Blood. https://doi.org/10.1182/blood-2008-06-161117
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