GATA-2 regulates granulocyte-macrophage progenitor cell function

Rodrigues, Neil ORCID: https://orcid.org/0000-0002-1925-7733, Boyd, Ashleigh S., Fugazza, Cristina, May, Gillian E., Guo, YanPing, Tipping, Alex J., Scadden, David T., Vyas, Paresh and Enver, Tariq 2008. GATA-2 regulates granulocyte-macrophage progenitor cell function. Blood 112 (13) , pp. 4862-4873. 10.1182/blood-2008-01-136564

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Abstract

The zinc finger transcription factor GATA-2 has been implicated in the regulation of hematopoietic stem cells. Herein, we explored the role of GATA-2 as a candidate regulator of the hematopoietic progenitor cell compartment. We showed that bone marrow from GATA-2 heterozygote (GATA-2+/−) mice displayed attenuated granulocyte-macrophage progenitor function in colony-forming cell (CFC) and serial replating CFC assays. This defect was mapped to the Lin−CD117+Sca-1−CD34+CD16/32high granulocyte-macrophage progenitor (GMP) compartment of GATA-2+/− marrow, which was reduced in size and functionally impaired in CFC assays and competitive transplantation. Similar functional impairments were obtained using a RNA interference approach to stably knockdown GATA-2 in wild-type GMP. Although apoptosis and cell-cycle distribution remained unperturbed in GATA-2+/− GMP, quiescent cells from GATA-2+/− GMP exhibited altered functionality. Gene expression analysis showed attenuated expression of HES-1 mRNA in GATA-2–deficient GMP. Binding of GATA-2 to the HES-1 locus was detected in the myeloid progenitor cell line 32Dcl3, and enforced expression of HES-1 expression in GATA-2+/− GMP rectified the functional defect, suggesting that GATA-2 regulates myeloid progenitor function through HES-1. These data collectively point to GATA-2 as a novel, pivotal determinant of GMP cell fate.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Biosciences Research Institutes & Centres > European Cancer Stem Cell Research Institute (ECSCRI)
Subjects:	Q Science > QH Natural history > QH301 Biology
Publisher:	American Society of Hematology
ISSN:	0006-4971
Last Modified:	22 Jun 2023 10:01
URI:	https://orca.cardiff.ac.uk/id/eprint/51137

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