GATA2 functions at multiple steps in hemangioblast development and differentiation
Molecular mechanisms that regulate the generation of hematopoietic and endothelial cells from mesoderm are poorly understood. To define the underlying mechanisms, we compared gene expression profiles between embryonic stem (ES) cell-derived hemangioblasts (Blast-Colony-Forming Cells, BL-CFCs) and th...
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| Veröffentlicht in: | Development (Cambridge) 2007-01, Vol.134 (2), p.393-405 |
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| creator | Lugus, Jesse J Chung, Yun Shin Mills, Jason C Kim, Shin-Il Grass, Jeff Kyba, Michael Doherty, Jason M Bresnick, Emery H Choi, Kyunghee |
| description | Molecular mechanisms that regulate the generation of hematopoietic and endothelial cells from mesoderm are poorly understood. To define the underlying mechanisms, we compared gene expression profiles between embryonic stem (ES) cell-derived hemangioblasts (Blast-Colony-Forming Cells, BL-CFCs) and their differentiated progeny, Blast cells. Bioinformatic analysis indicated that BL-CFCs resembled other stem cell populations. A role for Gata2 , one of the BL-CFC-enriched transcripts, was further characterized by utilizing the in vitro model of ES cell differentiation. Our studies revealed that Gata2 was a direct target of BMP4 and that enforced GATA2 expression upregulated Bmp4, Flk1 and Scl . Conditional GATA2 induction resulted in a temporal-sensitive increase in hemangioblast generation, precocious commitment to erythroid fate, and increased endothelial cell generation. GATA2 additionally conferred a proliferative signal to primitive erythroid progenitors. Collectively, we provide compelling evidence that GATA2 plays specific, contextual roles in the generation of Flk-1 + mesoderm, the Flk-1 + Scl + hemangioblast, primitive erythroid and endothelial cells. |
| doi_str_mv | 10.1242/dev.02731 |
| format | Article |
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To define the underlying mechanisms, we compared gene expression profiles between embryonic stem (ES) cell-derived hemangioblasts (Blast-Colony-Forming Cells, BL-CFCs) and their differentiated progeny, Blast cells. Bioinformatic analysis indicated that BL-CFCs resembled other stem cell populations. A role for Gata2 , one of the BL-CFC-enriched transcripts, was further characterized by utilizing the in vitro model of ES cell differentiation. Our studies revealed that Gata2 was a direct target of BMP4 and that enforced GATA2 expression upregulated Bmp4, Flk1 and Scl . Conditional GATA2 induction resulted in a temporal-sensitive increase in hemangioblast generation, precocious commitment to erythroid fate, and increased endothelial cell generation. GATA2 additionally conferred a proliferative signal to primitive erythroid progenitors. 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To define the underlying mechanisms, we compared gene expression profiles between embryonic stem (ES) cell-derived hemangioblasts (Blast-Colony-Forming Cells, BL-CFCs) and their differentiated progeny, Blast cells. Bioinformatic analysis indicated that BL-CFCs resembled other stem cell populations. A role for Gata2 , one of the BL-CFC-enriched transcripts, was further characterized by utilizing the in vitro model of ES cell differentiation. Our studies revealed that Gata2 was a direct target of BMP4 and that enforced GATA2 expression upregulated Bmp4, Flk1 and Scl . Conditional GATA2 induction resulted in a temporal-sensitive increase in hemangioblast generation, precocious commitment to erythroid fate, and increased endothelial cell generation. GATA2 additionally conferred a proliferative signal to primitive erythroid progenitors. 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| subjects | Animals Base Sequence Cell Differentiation Cells, Cultured Colony-Forming Units Assay DNA Primers - genetics Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Endothelial Cells - cytology Endothelial Cells - metabolism Erythroblasts - cytology Erythroblasts - metabolism GATA2 Transcription Factor - deficiency GATA2 Transcription Factor - genetics GATA2 Transcription Factor - metabolism Gene Expression Profiling Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Mesoderm - cytology Mesoderm - metabolism Mice Mice, Knockout Oligonucleotide Array Sequence Analysis Signal Transduction Vascular Endothelial Growth Factor Receptor-2 - genetics Vascular Endothelial Growth Factor Receptor-2 - metabolism |
| title | GATA2 functions at multiple steps in hemangioblast development and differentiation |
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