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Establishment of erythroleukemic GAK14 cells and characterization of GATA1 N-terminal domain
- Source :
- Genes to cells : devoted to molecularcellular mechanisms. 18(10)
- Publication Year :
- 2013
-
Abstract
- GATA1 is a transcription factor essential for erythropoiesis and megakaryopoiesis. It has been found that Gata1 gene knockdown heterozygous female (Gata1(G1.05/+)) mice spontaneously develop erythroblastic leukemias. In this study, we have generated a novel Gata1 knockdown erythroblastic cell line, designated GAK14, from the leukemia cells in the Gata1(G1.05/+) mice. Although GAK14 cells maintain immature phenotype on OP9 stromal cells in the presence of erythropoietin and stem cell factor, the cells produce Gr-1-, Mac1-, B220-, CD3e- or CD49b-positive hematopoietic cells when co-cultured with DAS104-8 feeder cells. However, GAK14 cells did not produce erythroid and megakaryocytic lineages, perhaps due to the absence of GATA1. Indeed, GAK14 cells became capable of differentiating into mature erythroid cells when complemented with full-length GATA1 and co-cultured with fetal liver-derived FLS5 stromal cells. This differentiation potential was impaired when GATA1 lacking the N-terminal domain was complemented. The N-terminal domain is known to contribute to the pathogenesis of transient abnormal myelopoiesis and acute megakaryoblastic leukemia related to Down syndrome. These results thus showed that GAK14 cells will serve as a powerful tool for dissecting domain function of GATA1 and that the GATA1 N-terminal domain is essential for the erythroid differentiation of GAK14 cells.
- Subjects :
- Stromal cell
Gene Expression
Stem cell factor
Mice
hemic and lymphatic diseases
Cell Line, Tumor
Genetics
Animals
Cell Lineage
Erythropoiesis
GATA1 Transcription Factor
Amino Acids
Megakaryocyte Progenitor Cells
Erythroid Precursor Cells
Myelopoiesis
CD40
biology
GATA2
GATA1
Cell Biology
Virology
Coculture Techniques
Cell biology
Protein Structure, Tertiary
Haematopoiesis
Cell culture
Gene Knockdown Techniques
biology.protein
Female
Leukemia, Erythroblastic, Acute
Subjects
Details
- ISSN :
- 13652443
- Volume :
- 18
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Genes to cells : devoted to molecularcellular mechanisms
- Accession number :
- edsair.doi.dedup.....853dc4c870a7af8da0014a1d57ed221c