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  • The EMBO Journal (2002) 21, 6700 - 6708
  • doi:10.1093/emboj/cdf674

SCL/tal-1-dependent process determines a competence to select the definitive hematopoietic lineage prior to endothelial differentiation

Mitsuhiro Endoh1, Minetaro Ogawa2, Stuart Orkin3 and Shin-ichi Nishikawa1

  1. Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto, 606-8057, Japan
  2. Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, 860-0811, Japan
  3. Division of Hematology/Oncology, Children's Hospital and Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA

Correspondence to:

Mitsuhiro Endoh, E-mail: mendoh@virus.kyoto-u.ac.jp

Received 20 September 2002; Accepted 22 October 2002; Revised 22 October 2002

Hematopoiesis in most vertebrate species occurs in two distinct phases, primitive and definitive, which diverge from FLK1+VE-cadherin- mesoderm and FLK1+VE-cadherin+ endothelial cells (EC), respectively. This study aimed at determining the stage at which hematopoietic lineage fate is determined by manipulating the SCL/tal-1 expression that is known to be essential for the early development of the primitive and definitive hematopoietic systems. We established SCL-null ES cell lines in which SCL expression is rescued by tamoxifen-inducible Cre recombinase-loxP site-mediated recombination. While no hematopoietic cells (HPC) were detected in SCL-null ES cell differentiation cultures, SCL gene reactivation from day 2 to day 4 after initiation of differentiation could rescue both primitive and definitive hematopoiesis. SCL reactivation at later phases was ineffective. Moreover, generation of VE-cadherin+ EC that can give rise to definitive HPC required SCL reactivation prior to VE-cadherin expression. These results indicated that the competence to become HPC is acquired at the mesodermal stage by a SCL-dependent process that takes place independently of determination of endothelial fate.

  • Keywords:

    • ES cell,
    • FLK1,
    • MerCreMer,
    • SCL,
    • tal-1,
    • VE-cadherin