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Enforced expression of the GATA-3 transcription factor affects cell fate decisions in hematopoiesis
Abstract
Objective Three GATA family transcription factors are involved in various aspects of hematopoiesis. Their lineage-restricted expression correlates well with their function in selective lineage commitment and differentiation. We focused on the role of GATA-3 to determine whether an intrinsic variation among different GATA proteins, in addition to the distinct expression pattern, determines lineage specification. Materials and methods Using a retroviral vector, we introduced the GATA-3 gene into primary murine hematopoietic stem cells (HSC) and examined their development in in vitro suspension culture and colony-forming assays as well as in vivo competitive repopulation studies. Results Although GATA-3 expression normally is restricted to lymphoid precursor and committed T cells, overexpression of GATA-3 in HSC results in cessation of cell expansion followed by selective induction of megakaryocytic and erythroid differentiation and inhibition of myeloid and lymphoid precursor development in liquid suspension culture and in vitro colony-forming assays. Competitive repopulation studies show that transplanted GATA-3-expressing HSC/progenitor cells give one wave of erythrocyte development but fail to expand in the bone marrow or to reconstitute other lineages. Conclusions The selective megakaryocytic/erythroid differentiation in HSC with enforced GATA-3 expression suggests a functional redundancy among GATA proteins and indicates that the specific lineage fate determination by indi…
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“The top 10 TF binding sites with the highest methylation increase in Tet2-KO relative to WT upon IL1β stimulation in CMPs included GATA1, TAL1, and MAZ which promote erythropoiesis (Fig. 4c)35–37.”
From Clonal hematopoiesis related TET2 loss-of-function impedes IL1β-mediated epigenetic reprogramming in hematopoietic stem and progenitor cells (2023) · cites this paper as [37]
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Challen, G. A., Sun, D., Jeong, M., Luo, M., Jelinek, J., Berg, J. S., Bock, C., Vasanthakumar, A., Gu, H., Xi, Y., et al. (2012) · Nature Genetics · doi:10.1038/ng.1009 · Cited by 1,122
Taghon, T., Yui, M. A., & Rothenberg, E. V. (2007) · Nature Immunology · doi:10.1038/ni1486 · Cited by 195
McClatchy, J., Strogantsev, R., Wolfe, E., Lin, H. Y., Mohammadhosseini, M., Davis, B. A., Eden, C., Goldman, D., Fleming, W. H., Conley, P., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43697-y · Cited by 95
Metadata
- Authors
- Chen, D., & Zhang, G.
- Venue
- Experimental Hematology
- Publisher
- Elsevier BV
- Published
- 2001-08
- Volume
- 29
- Issue
- 8
- Pages
- 971-980
- ISSN
- 0301-472X
- Cited by
- 63
- References
- 6
- Language
- en
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