Oct-3/4 Dose Dependently Regulates Specification of Embryonic Stem Cells toward a Cardiac Lineage and Early Heart Development
| Autor: | Michel Pucéat, Karim Chebli, Dana Zeineddine, Evangelia Papadimou, Atta Behfar, Valerie A. Wallace, Ilona S. Skerjanc, Sherry Thurig, Mathieu Gineste, Jun Liu, Corinne Grey |
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| Rok vydání: | 2006 |
| Předmět: |
Mesoderm
animal structures Microinjections DEVBIO Biology General Biochemistry Genetics and Molecular Biology Mice Organ Culture Techniques medicine Animals Inner cell mass Cell Lineage Myocytes Cardiac RNA Messenger RNA Small Interfering Molecular Biology In Situ Hybridization POU domain Heart development Stem Cells Gene Expression Regulation Developmental Heart Cell Biology Immunohistochemistry STEMCELL Embryonic stem cell Cell biology Blastocyst medicine.anatomical_structure Epiblast embryonic structures Immunology Stem cell Octamer Transcription Factor-3 Developmental Biology Morphogen |
| Zdroj: | Developmental Cell. 11:535-546 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2006.07.013 |
| Popis: | SummaryThe transcriptional mechanisms underlying lineage specification and differentiation of embryonic stem (ES) cells remain elusive. Oct-3/4 (POU5f1) is one of the earliest transcription factors expressed in the embryo. Both the pluripotency and the fate of ES cells depend upon a tight control of Oct-3/4 expression. We report that transgene- or TGFβ-induced increase in Oct-3/4 mRNA and protein levels in undifferentiated ES cells and at early stages of differentiation triggers expression of mesodermal and cardiac specific genes through Smad2/4. cDNA antisense- and siRNA-mediated inhibition of upregulation of Oct-3/4 in ES cells prevent their specification toward the mesoderm and their differentiation into cardiomyocytes. Similarly, Oct-3/4 siRNA injected in the inner cell mass of blastocysts impairs cardiogenesis in early embryos. Thus, quantitative Oct-3/4 expression is regulated by a morphogen, pointing to a pivotal and physiological function of the POU factor in mesodermal and cardiac commitments of ES cells and of the epiblast. |
| Databáze: | OpenAIRE |
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