Upon binding of a GWRQ peptide, HT-H cells became highly proliferative and motile. HT-H cells expressed ErbB family receptors and bound EGF and heparin-binding EGF-like growth factor (HB-EGF), but ErbB family receptor phosphorylation in these cells required GWRQ. In the absence of GWRQ, trophinin interacted with the cytoplasmic protein bystin, which binds to ErbB4 and blocks its autophosphorylation. In HT-H cells, GWRQ peptide dissociated trophinin from bystin, and ErbB4 was activated. Culturing monkey blastocysts in the presence of the peptide increased total number and motility of the trophectoderm cells. These results suggest that trophinin-mediated cell adhesion functions as a molecular switch for trophectoderm activation in human embryo implantation.BYSL ͉ ErbB4 ͉ pregnancy ͉ receptor tyrosine kinase ͉ stem cells
GATA-2 is a zinc finger transcription factor essential for differentiation of immature hematopoietic cells. We analyzed the function of GATA-2 by a combined method of tetracycline-dependent conditional gene expression and in vitro hematopoietic differentiation from mouse embryonic stem (ES) cells using OP9 stroma cells (OP9 system). In the presence of macrophage colony-stimulating factor (M-CSF), the OP9 system induced macrophage differentiation. GATA-2 expression in this system inhibited macrophage differentiation and redirected the fate of hematopoietic differentiation to other hematopoietic lineages. GATA-2 expression commencing at day 5 or day 6 induced megakaryocytic or erythroid differentiation, respectively. Expression levels of PU.1, a hematopoietic transcription factor that interferes with GATA-2, appeared to play a critical role in differentiation to megakaryocytic or erythroid lineages. Transcription of PU.1 was affected by histone acetylation induced by binding of GATA-2 to the PU.1 promoter region. This study demonstrates that the function of GATA-2 is modified in a context-dependent manner by expression of PU.1, which in turn is regulated by GATA-2.
GATA-1, a zinc finger transcription factor, has been believed to be indispensable for the survival of proerythroblasts. However, we found that GATA-1-null proerythroblasts could survive and proliferate on OP9 stroma cells in the presence of erythropoietin. Furthermore, myeloid and mast cells were induced from the GATA-1-null proerythroblasts by the stimulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), respectively, but lymphoid differentiation was not achieved by in vivo transfer. Thus, without activity of the transcription factor required for terminal differentiation, even relatively mature and committed cells proliferate continuously with the differentiation capacity to other lineages. Our data suggest that GATA-1 is a critical transcription factor to fix erythroid progenitors to the erythroid lineage.
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