Normal Hemopoiesis

Overexpression of a hematopoietic transcriptional regulator EDAG induces myelopoiesis and suppresses lymphopoiesis in transgenic mice

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Abstract

Erythroid differentiation-associated gene (EDAG) is a hematopoietic tissue-specific gene that is highly expressed in the earliest CD34+ lin bone marrow (BM) cells and involved in the proliferation and differentiation of hematopoietic cells. To investigate the role of EDAG in hematopoiesis, we established an EDAG transgenic mouse model driven by human CD11a promoter. The transgenic mice showed increased mortality with severe organ infiltration by neutrophils, and the homeostasis of hematopoiesis was broken. The myelopoiesis was enhanced with expansion of myeloid cells in BM, increased peripheral granulocytes and extramedullary myelopoiesis in spleen. In contrast to myeloid cells, the lymphoid commitment was severely impaired with the B lymphopoiesis blocked at the transition from pro/pre-B I to pre-B II stage in BM and T thymocytes development blocked at the most immature stage (DN I). Moreover, we showed that EDAG was a transcriptional regulator which had transactivation activity and regulated the expression of several key transcription factors such as PU.1 and Pax5 in transgenic hematopoietic stem cells. These data suggested that EDAG was a key transcriptional regulator in maintaining the homeostasis of hematopoietic lineage commitment.

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Acknowledgements

This work was partially supported by Chinese National Natural Science Foundation Projects (30321003), Chinese National Science Foundation Key Program Projects (30630035) and Chinese State Key Projects for Basic Research (2002CB513103). The authors have no conflicting financial interests.

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Correspondence to X-M Yang.

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Li, C., Zhan, Y., Li, W. et al. Overexpression of a hematopoietic transcriptional regulator EDAG induces myelopoiesis and suppresses lymphopoiesis in transgenic mice. Leukemia 21, 2277–2286 (2007) doi:10.1038/sj.leu.2404901

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Keywords

  • EDAG
  • myelopoiesis
  • lymphopoiesis
  • hematopoiesis
  • transactivator
  • lineage commitment

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