Differences in early lineage segregation between mammals

Kuijk, Ewart; Puy, Leonie du; Tol, Helena T A van; Oei, Christine; Haagsman, Henk P.; Colenbrander, B.; Roelen, Bernard A.J.

doi:10.1002/dvdy.21480

Cited by 189 publications

(205 citation statements)

References 45 publications

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“…Immunofluorescence studies demonstrate that Nanog expression cannot be detected in in vitro porcine blastocysts and Oct4 is not confined to the ICM, which is not identical with the studies in mouse (Kuijk et al, 2008). In this study, we find that there is expression of Nanog, Oct4, and Sox2 both in IVF and NT porcine embryos from 2-cell to morula stage, which keeps a comparatively stable level except there is an elevation of Nanog at 8-cell stage.…”

Section: Exogenous Nanog Activates Endogenous Oct4 Sox2 and Nanog Econtrasting

confidence: 72%

Overexpression Nanog Activates Pluripotent Genes in Porcine Fetal Fibroblasts and Nuclear Transfer Embryos

Zhang

Luo

Bou

et al. 2011

The Anatomical Record

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Nanog as an important transcription factor plays a pivotal role in maintaining pluripotency and in reprogramming the epigenome of somatic cells. Its ability to function on committed somatic cells and embryos has been well defined in mouse and human, but rarely in pig. To better understand Nanog's function on reprogramming in porcine fetal fibroblast (PFF) and nuclear transfer (NT) embryo, we cloned porcine Nanog CDS and constructed pcDNA3.1 (þ)/Nanog and pEGFP-C1/Nanog overexpression vectors and transfected them into PFFs. We studied the cell biological changes and the expression of Nanog, Oct4, Sox2, Klf4, C-myc, and Sall4 in transfected PFFs. We also detected the development potential of the cloned embryos harboring Nanog stably overexpressed fibroblasts and the expression of Oct4, Sox2, and both endogenous and exogenous Nanog in these embryos. The results showed that transient overexpression Nanog in PFF could activate the expression of Oct4 (5-fold), C-myc (2-fold), and Sall4 (5-fold) in somatic cells, but they could not be maintained during G418 selection. In NT embryos, although Nanog overexpression did not have a significant effect on blastocyst development rate and blastocyst cell number, it could significantly activate the expression of endogenous Nanog, Oct4, Sox2 to 160-fold, 93-fold, and 182-fold, respectively (P < 0.05). Our results demonstrate that Nanog could interact with and activate other pluripotent genes both in PFFs and embryos. Anat Rec, 294:1809Rec, 294: -1817Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.

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Section: Exogenous Nanog Activates Endogenous Oct4 Sox2 and Nanog Econtrasting

confidence: 72%

Overexpression Nanog Activates Pluripotent Genes in Porcine Fetal Fibroblasts and Nuclear Transfer Embryos

Zhang

Luo

Bou

et al. 2011

The Anatomical Record

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“…5C ). The meiotic marker SCYP3 [ 21 ], however, was not detected in these groups suggesting that extended cultures may be needed to initiate meiotic differentiation in vitro. These results indicate that pEpiSC have the potential to initiate the germ cell program upon induction with BMP-4.…”

Section: Maintenance Of Self-renewalmentioning

confidence: 86%

Pig Epiblast Stem Cells Depend on Activin/Nodal Signaling for Pluripotency and Self-Renewal

Alberio

Croxall

Allegrucci

2010

Stem Cells and Development

106

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Activin/Nodal signaling is required for maintaining pluripotency and self-renewal of mouse epiblast stem cells and human embryonic stem cells (hESC). In this study, we investigated whether this signaling mechanism is also operative in cultured epiblasts derived from Days 10.5-12 pig embryos. Pig epiblast stem cell lines (pEpiSC) were established on mouse feeder layers and medium supplemented with basic fi broblast growth factor (bFGF). pEpiSC express the core pluripotency factors OCT4 (or POU5F1 ), NANOG , SOX2 , and NODAL , but they do not express REX1 or alkaline phosphatase activity. Blocking leukemia inhibitory factor (LIF)/JAK/STAT3 pathway by adding the specifi c JAK I inhibitor 420099 and an anti-LIF antibody over 3 passages did not affect pluripotency of pEpiSC. In contrast, cells grown with the Alk-5 inhibitor SB431542, which blocks Activin/Nodal pathway, differentiated readily toward the neural lineage. pEpiSC are pluripotent, as established by their differentiation potential to ectoderm, mesoderm, and endoderm. These cells can be induced to differentiate toward trophectoderm and to germ cell precursors in response to bone morphogenetic protein 4 (BMP-4). In conclusion, our study demonstrates that pig epiblasts express the core pluripotency genes and that the capacity for maintaining self-renewal in pEpiSC depends on Activin/Nodal signaling. This study provides further evidence that maintenance of pluripotency via Activin/Nodal signal is conserved in mammals. Introduction Mouse embryonic stem cells (mESC), conventionally derived from the inner cell mass (ICM) of preimplantation blastocysts, are pluripotent and can self-renew indefinitely in culture. mESC depend on the cytokines leukemia inhibitory factor (LIF) and bone morphogenetic protein 4 (BMP-4) to maintain the undifferentiated state [ 1 , 2 ]. Human embryonic stem cells (hESC) are also derived from blastocysts; however, these cells depend on basic fi broblast growth factor (bFGF) and Activin A for pluripotency and selfrenewal [ 3 , 4 ]. Interestingly, pluripotent cells derived from mouse epiblasts, a part of the ICM, also require bFGF and Activin A for pluripotency and self-renewal [ 5 , 6 ]. hESC share multiple features with mouse epiblast stem cells (mEpiSC), such as growing as fl at and compact colonies [5][6][7], they respond to BMP-4 by differentiating to trophectoderm (TE) [ 8 ] and germ cell progenitors [ 9 ], and they do not require LIF/ JAK/STAT3 signaling for self-renewal [ 4 , 10 ]. The functional and phenotypic similarities between these cell types suggest a developmental relationship [ 5 , 6 ], and demonstrate that there are at least 2 signaling mechanisms involved in capturing pluripotency in vitro. Recent reports show that bFGF and Activin A are also necessary for maintaining rabbit ESC [ 11 , 12 ], indicating that this signaling pathway may be a conserved mechanism of pluripotency in mammals.Here we tested this hypothesis in pigs, a representative of ungulates. Attempts to derive stem cells from pig embryos have traditionally reli...

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“…At the morula-to-blastocyst transition, mammalian embryos undergo the first lineage segregation into the inner cell mass (ICM) and trophectoderm (TE) [27,28]. The repression of morula-to-blastocyst transition by ethionine prompted us to investigate the expression levels of cell lineagerelated transcription factors involved in blastocyst formation.…”

Section: Discussionmentioning

confidence: 99%

“…Oct4 likely functions primarily as the first determinant of ICM cell lineage by preventing their differentiation into TE cells, while Nanog is thought to act as a crucial keeper of pluripotency of some ICM cells (epiblast) by preventing their differentiation into primitive endoderm cells [29,30]. Although the localization of OCT4 and CDX2 in the ICM and TE and/or their contributions to ICM/TE lineage segregation are different between mouse and bovine blastocysts [21,28,31,32], NANOG expression has been shown to be confined to the ICM also in bovine blastocysts at least in the spherical stage [21,28,31], and its expression is likely to be implicated in ICM lineage determination also in the bovine [28]. Forced overexpression of Nanog in mouse ES cells led to autonomous self-renewal of the cells with retention of the undifferentiated state [29].…”

Section: Discussionmentioning

confidence: 99%

Importance of Methionine Metabolism in Morula-to-blastocyst Transition in Bovine Preimplantation Embryos

Ikeda

Sugimoto

Kume

2012

Journal of Reproduction and Development

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Abstract. The roles of methionine metabolism in bovine preimplantation embryo development were investigated by using ethionine, an antimetabolite of methionine. In vitro produced bovine embryos that had developed to the 5-cell stage or more at 72 h after the commencement of in vitro fertilization (IVF) were then cultured until day 8 (IVF = day 0) in medium supplemented with 0 (control), 1, 5 and 10 mM ethionine. Compared with the blastocyst development in the control (40.0%), ethionine at 10 mM almost completely blocked blastocyst development (1.1%, P<0.001), and this concentration was used in the following experiments. Methionine added at the same concentration (10 mM, a concentration control of ethionine) did not cause such an intense developmental inhibition. Development to the compacted morula stage on day 6 was not affected by 10 mM ethionine treatment. S-adenosylmethionine (SAM) added to the ethionine treatment partly restored the blastocyst development. Semiquantitative reverse transcription-polymerase chain reaction analysis of cell lineage-related transcription factors in day 6 compacted morulae showed that the expressions of NANOG and TEAD4 were increased by ethionine treatment relative to the control (P<0.01). Furthermore, immunofluorescence analysis of 5-methylcytosine revealed that DNA was hypomethylated in the ethionine-treated day 6 morulae compared with the control (P<0.001). These results demonstrate that the disruption of methionine metabolism causes impairment of the morula-toblastocyst transition during bovine preimplantation development in part via SAM deficiency, indicating the indispensable roles of methionine during this period. The disruption of methionine metabolism may cause hypomethylation of DNA and consequently lead to the altered expression of developmentally important genes, which then results in the impairment of blastocyst development. Key words: Bovine, Methionine, One-carbon metabolism, Preimplantation embryo, S-adenosylmethionine (J. Reprod. Dev. 58: [91][92][93][94][95][96][97] 2012) M ethionine is a dietary essential amino acid that plays multiple biological roles, including those as the initiating amino acid in eukaryotic protein synthesis, a precursor of the essential methyl donor for methylation reactions (S-adenosylmethionine, SAM) and a source of redox regulators (cysteine and glutathione) [1,2]. Methionine metabolism can be seen as the trans-and remethylation cycle of methionine (methionine cycle) that intertwines with the cycle of folate metabolism (folate cycle) and the transsulfuration pathway from homocysteine, an intermediate in the methionine cycle [3], and these combined metabolic networks are called one-carbon metabolism [4,5]. Recently, mammalian oocytes and preimplantation embryos have been reported to express the key regulatory enzymes in one-carbon metabolism [6][7][8], suggesting that mammalian oocytes and preimplantation embryos can independently utilize and metabolize nutrients in one-carbon metabolism, such as methionine, choline, betaine, folates a...

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Differences in early lineage segregation between mammals

Cited by 189 publications

References 45 publications

Overexpression Nanog Activates Pluripotent Genes in Porcine Fetal Fibroblasts and Nuclear Transfer Embryos

Overexpression Nanog Activates Pluripotent Genes in Porcine Fetal Fibroblasts and Nuclear Transfer Embryos

Pig Epiblast Stem Cells Depend on Activin/Nodal Signaling for Pluripotency and Self-Renewal

Importance of Methionine Metabolism in Morula-to-blastocyst Transition in Bovine Preimplantation Embryos

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