Cross-regulation of the Nanog and Cdx2 promoters

Chen, Lingyi; Yabuuchi, Akiko; Eminli, Sarah; Takeuchi, Akari; Lu, Chi-Wei; Hochedlinger, Konrad; Daley, George Q.

doi:10.1038/cr.2009.79

Cited by 107 publications

(118 citation statements)

References 23 publications

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“…Cdx2 expression is directly repressed by Oct4 or Nanog, and repression of Nanog or Oct4 expression was shown to enhance Cdx2 expression (14,46). In our study, decreased SMAD2 expression in hESCs resulted in repression of NANOG and OCT4 expression and enhanced CDX2 expression through increased BMP signaling.…”

Section: Activation Of Nanog Expression and Suppression Of Bmp Signalmentioning

confidence: 57%

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Smad2 Is Essential for Maintenance of the Human and Mouse Primed Pluripotent Stem Cell State

Sakaki-Yumoto

Liu

Ramalho-Santos

et al. 2013

Journal of Biological Chemistry

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Background: TGF-␤ signaling is required for primed pluripotency, but the roles of Smad2 and Smad3 have not been well defined. Results: Smad2, but not Smad3, has a role in pluripotency by activating Nanog expression and repressing BMP signaling. Conclusion: Smad2 is essential in the maintenance of pluripotency. Significance: The roles of Smad2 and Smad3 need to be distinguished in the regulation of pluripotency by TGF-␤ signaling.

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Section: Activation Of Nanog Expression and Suppression Of Bmp Signalmentioning

confidence: 57%

“…Furthermore, Cdx2 binds Oct4 and Nanog gene promoter sequences, and Oct4 and Nanog can bind the Cdx2 promotor, conferring reciprocal repression (14,46). Therefore, decreased OCT4 expression in hESCs with decreased SMAD2 expression (Fig.…”

Section: Suppressing Cdx2 Expression Rescues Decreased Oct4 But Not mentioning

confidence: 99%

Smad2 Is Essential for Maintenance of the Human and Mouse Primed Pluripotent Stem Cell State

Sakaki-Yumoto

Liu

Ramalho-Santos

et al. 2013

Journal of Biological Chemistry

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“…CDX2 expression was found to be directly related to IFNτ expression along with the embryo development until the hatching stage in both BT-and AF-derived blastocysts suggesting that CDX2 is a potent regulator of IFNτ expression [22,33,34] while it showed no change in IVF-produced blastocysts.…”

Section: Discussionmentioning

confidence: 98%

Embryonic Development and Implantation Related Gene Expression of Oocyte Reconstructed with Bovine Trophoblast Cells

Saadeldin

Choi

Torre

et al. 2012

Journal of Reproduction and Development

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Abstract. The temporal progressive increase of interferon tau (IFNτ) secretion from the bovine trophoblast is a major embryonic signal of establishing pregnancy. Here, we cultured and isolated bovine trophoblast cells (BTs) from IVM/IVF oocytes and in vitro produced blastocysts, used them, for the first time, as donor cells for nuclear transfer and compared them with adult fibroblasts (AFs) as donor cells. BTs were reprogrammed in enucleated oocytes to blastocysts with similar efficiency to AFs (14.5% and 15.6% respectively, P≤0.05). The levels of IFNτ, CDX2 and OCT4 expression in IVF-, BTand AF-derived blastocysts were analyzed using reverse transcription polymerase chain reaction and reverse transcription quantitative polymerase chain reaction (RT-PCR and RT-qPCR). IVF-produced embryos were used as reference to analyze the linear progressive expression of IFNτ through mid, expanded and hatching blastocysts. RT-PCR and RT-qPCR studies showed that IFNτ expression was higher in BT-derived blastocysts than IVF-and AF-derived blastocysts. Both IVF-and BT-derived blastocysts showed a progressive increase in IFNτ expression as blastocyst development advanced when it compared with AF-derived blastocysts. OCT4 was inversely related with IFNτ expression, while CDX2 was found to be directly related with IFNτ temporal expression. Persistence of high expression of IFNτ and CDX2 was found to be higher in BT-derived embryos than in IVF-or AF-derived embryos. In conclusion, using BTs expressing IFNτ as donor cells for bovine NT could be a useful tool for understanding the IFNτ genetics and epigenetics. Key words: Bovine trophoblast, Interferon tau, Nuclear transfer, Real-time PCR, Reprogramming (J. Reprod. Dev. 58: [425][426][427][428][429][430][431] 2012) S ince the first cloned lamb was born, nuclear transfer (NT) has been challenging in several species and has produced many cloned offspring [1][2][3]. To produce cloned offspring, fetal fibroblasts have been chosen as a preferential donor cell line for NT so far because they have high proliferative potentials [4][5][6][7]. In cattle, fetal and adult fibroblasts have been dominantly used for NT to produce cloned calves. Additionally, several types of cells, like granulosa, cumulus, oviduct epithelial cells, skin, tongue and other cells, have been used for NT [8,9].After fertilization of an egg with a sperm, the one-cell stage embryo grow up through several mitosis and reaches the preimplantation stage, becoming a blastocyst, which consists of an inner cell mass (ICM) that is capable of differentiation into all embryo organs and trophoblasts, which are the first differentiated cells from the embryo, and contributes formation of the placenta and fetal membranes but does not participate the formation of the fetus proper [7]. Some reports have demonstrated trophoblast isolation and its function in vitro in cattle [10][11][12]. In mice, living pups were born by nuclear transfer of trophectoderm cells from the expanded blastocysts into enucleated oocytes [13] as a trial to show...

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“…The maintenance of pluripotency depends on OCT4 and NANOG functions during preimplantation development (Chen et al, 2009;Mitsui et al, 2003;Nichols et al, 1998;Shao et al, 2008). Pou5f1 and Nanog, both of which are ICM markers, negatively interact with Cdx2, a TE marker, and these three genes are key regulators in cell fate specification (Chen et al, 2009;Niwa et al, 2005;Ralston et al, 2010;Strumpf et al, 2005). Pou5f1 or Nanog knockout mouse embryos can develop into morphologically normal blastocysts; however, developmental arrest occurs during the postimplantation period due to a loss of pluripotency (Mitsui et al, 2003;Nichols et al, 1998;Ralston et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, we showed that the rescue of HMGPI had no effect on Klf5 expression in Chd1-knockdown-Hmgpi-rescue embryos, suggesting that there is no direct interaction between Hmgpi and Klf5 during preimplantation development. The maintenance of pluripotency depends on OCT4 and NANOG functions during preimplantation development (Chen et al, 2009;Mitsui et al, 2003;Nichols et al, 1998;Shao et al, 2008). Pou5f1 and Nanog, both of which are ICM markers, negatively interact with Cdx2, a TE marker, and these three genes are key regulators in cell fate specification (Chen et al, 2009;Niwa et al, 2005;Ralston et al, 2010;Strumpf et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

CHD1 acts via the Hmgpi pathway to regulate mouse early embryogenesis

Suzuki

Nozawa

Tsukamoto³

et al. 2015

Development

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The protein CHD1 is a member of the family of ATPase-dependent chromatin remodeling factors. CHD1, which recognizes trimethylated histone H3 lysine 4, has been implicated in transcriptional activation in organisms ranging from yeast to humans. It is required for pre-mRNA maturation, maintenance of mouse embryonic stem cell pluripotency and rapid growth of the mouse epiblast. However, the function(s) of CHD1 in mouse preimplantation embryos has not yet been examined. Here, we show that loss of CHD1 function led to embryonic lethality after implantation. In mouse embryos in which Chd1 was targeted by siRNA microinjection, the expression of the key regulators of cell fate specification Pou5f1 (also known as Oct4), Nanog and Cdx2 was dramatically decreased, starting at mid-preimplantation gene activation (MGA). Moreover, expression of Hmgpi and Klf5, which regulate Pou5f1, Nanog and Cdx2, was also significantly suppressed at zygotic gene activation (ZGA). Suppression of Hmgpi expression in Chd1-knockdown embryos continued until the blastocyst stage, whereas suppression of Klf5 expression was relieved by the morula stage. Next, we rescued HMGPI expression via Hmgpi mRNA microinjection in Chd1-knockdown embryos. Consequently, Pou5f1, Nanog and Cdx2 expression was restored at MGA and live offspring were recovered. These findings indicate that CHD1 plays important roles in mouse early embryogenesis via activation of Hmgpi at ZGA.

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Cross-regulation of the Nanog and Cdx2 promoters

Cited by 107 publications

References 23 publications

Smad2 Is Essential for Maintenance of the Human and Mouse Primed Pluripotent Stem Cell State

Smad2 Is Essential for Maintenance of the Human and Mouse Primed Pluripotent Stem Cell State

Embryonic Development and Implantation Related Gene Expression of Oocyte Reconstructed with Bovine Trophoblast Cells

CHD1 acts via the Hmgpi pathway to regulate mouse early embryogenesis

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