Oct-3/4 Dose Dependently Regulates Specification of Embryonic Stem Cells toward a Cardiac Lineage and Early Heart Development

• Published in: Developmental cell Vol. 11; no. 4; pp. 535 - 546
• Main Authors: Zeineddine, Dana, Papadimou, Evangelia, Chebli, Karim, Gineste, Mathieu, Liu, Jun, Grey, Corinne, Thurig, Sherry, Behfar, Atta, Wallace, Valerie A., Skerjanc, Ilona S., Pucéat, Michel
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 01.10.2006; Cell Press
• Subjects: Animals; Biological and medical sciences; Blastocyst - cytology; Blastocyst - metabolism; Cell differentiation, maturation, development, hematopoiesis; Cell Lineage; Cell physiology; DEVBIO; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Heart - growth & development; Immunohistochemistry; In Situ Hybridization; Mice; Microinjections; Molecular and cellular biology; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Organ Culture Techniques; RNA, Messenger - biosynthesis; RNA, Small Interfering - metabolism; Stem Cells - cytology; Stem Cells - physiology; STEMCELL; STEMCELL; DEVBIO; Heart; Regulation(control); Embryonic cell; Stem cell; Development; Early; Circulatory system
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2006.07.013

The 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.