The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells.
Embryonic stem (ES) cells derived from the inner cell mass (ICM) of blastocysts grow infinitely while maintaining pluripotency. Leukemia inhibitory factor (LIF) can maintain self-renewal of mouse ES cells through activation of Stat3. However, LIF/Stat3 is dispensable for maintenance of ICM and human ES cells, suggesting that the pathway is not fundamental for pluripotency. In search of a critical factor(s) that underlies pluripotency in both ICM and ES cells, we performed in silico differential display and identified several genes specifically expressed in mouse ES cells and preimplantation embryos. We found that one of them, encoding the homeoprotein Nanog, was capable of maintaining ES cell self-renewal independently of LIF/Stat3. nanog-deficient ICM failed to generate epiblast and only produced parietal endoderm-like cells. nanog-deficient ES cells lost pluripotency and differentiated into extraembryonic endoderm lineage. These data demonstrate that Nanog is a critical factor underlying pluripotency in both ICM and ES cells.
Mitsui
Kaoru
K
Laboratory of Animal Molecular Technology, Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Nara 630-0192, Japan.
Tokuzawa
Yoshimi
Y
Itoh
Hiroaki
H
Segawa
Kohichi
K
Murakami
Mirei
M
Takahashi
Kazutoshi
K
Maruyama
Masayoshi
M
Maeda
Mitsuyo
M
Yamanaka
Shinya
S
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018390:Gene Targeting; D018398:Homeodomain Proteins / Q000235:genetics / Q000302:isolation & purification*; D051379:Mice / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D000071317:Nanog Homeobox Protein; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000378:metabolism / Q000494:pharmacology
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators