Establishment of erythroleukemic GAK14 cells and characterization of GATA1 N-terminal domain

Harumi Y. Mukai, Mikiko Suzuki, Masumi Nagano, Shin'ya Ohmori, Akihito Otsuki, Kouhei Tsuchida, Takashi Moriguchi, Kinuko Ohneda, Ritsuko Shimizu, Osamu Ohneda, Masayuki Yamamoto

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

GATA1 is a transcription factor essential for erythropoiesis and megakaryopoiesis. It has been found that Gata1 gene knockdown heterozygous female (Gata1G1.05/+) 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 Gata1G1.05/+ 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.

Original languageEnglish
Pages (from-to)886-898
Number of pages13
JournalGenes to Cells
Volume18
Issue number10
DOIs
Publication statusPublished - 2013 Oct

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Establishment of erythroleukemic GAK14 cells and characterization of GATA1 N-terminal domain'. Together they form a unique fingerprint.

Cite this