Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis
| Autor: | Leonard I. Zon, Owen J. Tamplin, Paul F. McBride, Kelli J. Carroll, Dhvanit I. Shah, Diana S. Branco, Ebrahim Shafizadeh, Gordon J. Hildick-Smith, Heidi Anderson, Clara Wong, Trista E. North, Barry H. Paw, Jeffrey D. Cooney, Patrick G. Gallagher, Arthur J. Dalton, George C. Shaw |
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| Rok vydání: | 2013 |
| Předmět: |
LMO2
Embryo Nonmammalian animal structures Myeloid Hematopoietic System Molecular Sequence Data Biology Models Biological Article Evolution Molecular 03 medical and health sciences 0302 clinical medicine medicine Animals Erythropoiesis Amino Acid Sequence Cloning Molecular Primitive and definitive hematopoiesis Progenitor cell Molecular Biology Transcription factor Zebrafish Conserved Sequence 030304 developmental biology Genetics 0303 health sciences fungi Gene Expression Regulation Developmental Epistasis Genetic GATA1 Cell Biology Zebrafish Proteins Hematopoietic Stem Cells biology.organism_classification Lineage commitment Hematopoiesis DNA-Binding Proteins Haematopoiesis medicine.anatomical_structure Differentiation 030220 oncology & carcinogenesis Stem cell Developmental Biology |
| Zdroj: | Developmental Biology. 373:431-441 |
| ISSN: | 0012-1606 |
| Popis: | Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification. In mammals, Gfi1a regulates hematopoietic stem cells (HSC), myeloid and lymphoid populations, while its paralog, Gfi1b, regulates HSC, megakaryocyte and erythroid development. In zebrafish, gfi1aa is essential for primitive hematopoiesis; however, little is known about the role of gfi1aa in definitive hematopoiesis or about additional gfi factors in zebrafish. Here, we report the isolation and characterization of an additional hematopoietic gfi factor, gfi1b. We show that gfi1aa and gfi1b are expressed in the primitive and definitive sites of hematopoiesis in zebrafish. Our functional analyses demonstrate that gfi1aa and gfi1b have distinct roles in regulating primitive and definitive hematopoietic progenitors, respectively. Loss of gfi1aa silences markers of early primitive progenitors, scl and gata1. Conversely, loss of gfi1b silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for definitive hematopoiesis. We determine the epistatic relationships between the gfi factors and key hematopoietic transcription factors, demonstrating that gfi1aa and gfi1b join lmo2, scl, runx-1 and c-myb as critical regulators of teleost HSPC. Our studies establish a comparative paradigm for the regulation of hematopoietic lineages by gfi transcription factors. |
| Databáze: | OpenAIRE |
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