Premium
SCL/tal‐1‐dependent process determines a competence to select the definitive hematopoietic lineage prior to endothelial differentiation
Author(s) -
Endoh Mitsuhiro,
Ogawa Minetaro,
Orkin Stuart,
Nishikawa Shinichi
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf674
Subject(s) - biology , haematopoiesis , lineage (genetic) , microbiology and biotechnology , mesoderm , cellular differentiation , precursor cell , cre recombinase , genetics , immunology , gene , stem cell , cell , embryonic stem cell , transgene , genetically modified mouse
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.