Reference - Detail
|Author||Hirabayashi R, Hozumi S, Higashijima S, Kikuchi Y.|
|Title||Ddx46 is required for multi-lineage differentiation of hematopoietic stem cells in zebrafish.|
|Journal||Stem Cells Dev.|
Balanced and precisely controlled processes between self-renewal and differentiation of hematopoietic stem cells (HSCs) into all blood lineages are critical for vertebrate definitive hematopoiesis. However, the molecular mechanisms underlying the maintenance and differentiation of HSCs have not been fully elucidated. Here, we show that zebrafish Ddx46, encoding a DEAD-box RNA helicase, is expressed in HSCs of the caudal hematopoietic tissue (CHT). The number of HSCs expressing the molecular markers cmyb or T-cell acute lymphocytic leukemia 1 (tal1) was markedly reduced in Ddx46 mutants. However, massive cell death of HSCs was not detected, and proliferation of HSCs was normal in the CHT of the mutants at 48 h postfertilization. We found that myelopoiesis occurred, but erythropoiesis and lymphopoiesis were suppressed, in Ddx46 mutants. Consistent with these results, the expression of spi1, encoding a regulator of myeloid development, was maintained, but the expression of gata1a, encoding a regulator of erythrocyte development, was downregulated in the mutants. Taken together, our results provide the first genetic evidence that zebrafish Ddx46 is required for the multilineage differentiation of HSCs during development, through the regulation of specific gene expressions.
|MeSH||Animals Basic Helix-Loop-Helix Transcription Factors / biosynthesis Cell Differentiation / genetics Cell Proliferation DEAD-box RNA Helicases / biosynthesis DEAD-box RNA Helicases / genetics DEAD-box RNA Helicases / metabolism* Down-Regulation Erythropoiesis / genetics GATA1 Transcription Factor / biosynthesis Gene Expression Regulation, Developmental / genetics* Hematopoietic Stem Cells / cytology Hematopoietic Stem Cells / metabolism* Lymphopoiesis / genetics Mutation Myelopoiesis / genetics* Proto-Oncogene Proteins / biosynthesis RNA Splicing / genetics T-Cell Acute Lymphocytic Leukemia Protein 1 Trans-Activators / biosynthesis Zebrafish / genetics Zebrafish Proteins / biosynthesis Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*|
|WOS Category||MEDICINE, RESEARCH & EXPERIMENTAL TRANSPLANTATION HEMATOLOGY CELL & TISSUE ENGINEERING|