Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.
Oct4 is a mammalian POU transcription factor expressed by early embryo cells and germ cells. We report that the activity of Oct4 is essential for the identity of the pluripotential founder cell population in the mammalian embryo. Oct4-deficient embryos develop to the blastocyst stage, but the inner cell mass cells are not pluripotent. Instead, they are restricted to differentiation along the extraembryonic trophoblast lineage. Furthermore, in the absence of a true inner cell mass, trophoblast proliferation is not maintained in Oct4-/- embryos. Expansion of trophoblast precursors is restored, however, by an Oct4 target gene product, fibroblast growth factor-4. Therefore, Oct4 also determines paracrine growth factor signaling from stem cells to the trophectoderm.
Nichols
J
J
Centre for Genome Research, University of Edinburgh, United Kingdom.
Zevnik
B
B
Anastassiadis
K
K
Niwa
H
H
Klewe-Nebenius
D
D
Chambers
I
I
Schöler
H
H
Smith
A
A
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004475:Ectoderm / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D005314:Embryonic and Fetal Development; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D007633:Keratins / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D050814:Octamer Transcription Factor-3; D019899:Paracrine Communication; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D004268:DNA-Binding Proteins; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D005346:Fibroblast Growth Factors; D007633:Keratins