Proper levels of c-Myb are discretely defined at distinct steps of hematopoietic cell development

Research output: Contribution to journalArticle

Authors

  • H Sakamoto
  • G Dai
  • K Tsujino
  • K Hashimoto
  • X Huang
  • T Fujimoto
  • M Mucenski
  • M Ogawa

Abstract

The definitive hematopoietic cell lineages have been proposed to originate from hemogenic endothelial cells during mouse embryogenesis. c-Myb is a transcription factor that is essential for the development of definitive hematopoiesis. To investigate the functional role of c-Myb in hematopoietic cell development from endothelial cells, we introduced a c-myb transgene expressed under the control of a tetracycline-regulated promoter into the c-myb(-/-) embryonic stem (ES) cell line, with the aim of inducing c-Myb expression at any stage and at any level. Induction of c-Myb expression after replating c-myb(-)(/)(-) endothelial cells rescued the generation and proliferation of definitive hematopoietic progenitor cells, suggesting that c-Myb expression in developing endothelial cells is not a prerequisite for their hematogenic potential. Overexpression of c-Myb, however, prevented the terminal differentiation of erythrocytes and megakaryocytes and completely abolished B-lymphocyte development. Our results indicate that c-Myb is a major factor that controls differentiation as well as proliferation of hematopoietic progenitor cells derived from hemogenic endothelial cells, and that appropriate levels of c-Myb protein are strictly defined at distinct differentiation steps of each hematopoietic cell lineage.

Details

Original languageEnglish
Pages (from-to)896-903
Number of pages8
JournalBlood
Volume108
Issue number3
Publication statusPublished - 1 Aug 2006