Oct-3/4 dose dependently regulates specification of embryonic stem cells toward a cardiac lineage and early heart development.
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 TGFbeta-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.
Zeineddine
Dana
D
CNRS FRE2593, CRBM, 34293 Montpellier, France.
Papadimou
Evangelia
E
Chebli
Karim
K
Gineste
Mathieu
M
Liu
Jun
J
Grey
Corinne
C
Thurig
Sherry
S
Behfar
Atta
A
Wallace
Valerie A
VA
Skerjanc
Ilona S
IS
Pucéat
Michel
M
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008845:Microinjections; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering