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• W3119368422 abstract "Lysophosphatidic acid (LPA) is one of the lipids identified to be involved in stem cell differentiation. It exerts various functions through activation of G protein-coupled lysophosphatidic acid receptors (LPARs). In previous studies, we have demonstrated that activation of LPA receptor 3 (LPA 3 ) promotes erythropoiesis of human hematopoietic stem cells (HSCs) and zebrafish using molecular and pharmacological approaches. Our results show that treatment with lysophosphatidic acid receptor 2 (LPA 2 ) agonist suppressed erythropoiesis, whereas activation of LPA 3 by 1-oleoyl-2-methyl-sn-glycero-3-phosphothionate (2S-OMPT) promoted it, both in vitro and in vivo. Furthermore, we have demonstrated the inhibitory role of LPA 3 during megakaryopoiesis. However, the mechanism underlying these observations remains elusive. In the present study, we suggest that the expression pattern of LPARs may be correlated with the transcriptional factors GATA-1 and GATA-2 at different stages of myeloid progenitors. We determined that manipulation of GATA factors affected the expression levels of LPA 2 and LPA 3 in K562 leukemia cells. Using luciferase assays, we demonstrate that the promoter regions of LPAR2 and LPAR3 genes were regulated by these GATA factors in HEK293T cells. Mutation of GATA-binding sites in these regions abrogated luciferase activity, suggesting that LPA 2 and LPA 3 are regulated by GATA factors. Moreover, physical interaction between GATA factors and the promoter region of LPAR genes was verified in K562 cells using chromatin immunoprecipitation (ChIP) studies. Taken together, our results suggest that balance between LPA 2 and LPA 3 expression, which may be determined by GATA factors, is a regulatory switch for lineage commitment in myeloid progenitors. The expression-level balance of LPA receptor subtypes represents a novel mechanism regulating erythropoiesis and megakaryopoiesis." @default.
• W3119368422 created "2021-01-18" @default.
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• W3119368422 date "2021-04-01" @default.
• W3119368422 modified "2023-09-24" @default.
• W3119368422 title "Transcriptional regulation of lysophosphatidic acid receptors 2 and 3 regulates myeloid commitment of hematopoietic stem cells" @default.
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• W3119368422 doi "https://doi.org/10.1152/ajpcell.00506.2020" @default.
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