OCT4/POU5F1 is required for NANOG expression in bovine blastocysts

Simmet, Kilian; Zakhartchenko, Valeri; Philippou‐Massier, Julia; Blum, Helmut; Klymiuk, Nikolai; Wolf, Eckhard

doi:10.1073/pnas.1718833115

Cited by 94 publications

(120 citation statements)

References 46 publications

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“…Furthermore, the TE cells of an early bovine blastocyst (7 dpi) retain the ability to contribute to the ICM derivatives in chimaeras. In support of this data, a recent study by Simmet and colleagues (Simmet et al, 2018) reports that the deletion of the OCT4 gene (by the CRISPR-Cas9 system) in bovine embryos did not affect the CDX2 expression in the TE. Control blastocysts showed a typical salt-and-pepper distribution of NANOG and GATA6 positive cells in the ICM, a pattern similar to that previously described in the mouse (Chazaud et al, 2006, Plusa et al, 2008.…”

Section: Mechanisms Of Pluripotency Maintenance In Cattlesupporting

confidence: 62%

Beyond the mouse: non-rodent animal models for study of early mammalian development and biomedical research

Madeja

Pawlak²,

Piliszek³

2019

Int. J. Dev. Biol.

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The preimplantation development of mammals generally follows the same plan. It starts with the formation of a totipotent zygote, and through consecutive cleavage divisions and differentiation events leads to blastocyst formation. However, the intervening events may differ between species. The regulation of these processes has been extensively studied in the mouse, which displays some unique features among eutherian mammals. Farm animals such as pigs, cattle, sheep and rabbits share several similarities with one another, and with the human developmental plan. These include the timing of epigenetic reprogramming, the moment of embryonic genome activation and the developmental time-frame. Recently, efficient techniques for genetic modification have been established for large domestic animals. Genome sequences and gene manipulation tools are now available for cattle, pigs, sheep and goats, and a larger number of genetically engineered livestock is now accessible for biomedical research. Yet, these animals still make up less than 0.5% of animals in research, mainly due to our inadequate knowledge of the processes responsible for pluripotency maintenance (to date no stable naïve embryonic stem cell lines have been established) and early development. In this review, we highlight our present knowledge of the key preimplantation events in the 3 non-rodent species which present the highest potential for biomedical research related to early embryonic development: cattle, which offer an excellent model to study human in vitro embryo development, pigs which emerge as models to study the long-term effects of gene-based therapies and rabbits, which in many aspects of embryology resemble the human.

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Section: Mechanisms Of Pluripotency Maintenance In Cattlesupporting

confidence: 62%

Beyond the mouse: non-rodent animal models for study of early mammalian development and biomedical research

Madeja

Pawlak²,

Piliszek³

2019

Int. J. Dev. Biol.

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“…Although the mechanisms by which nuclear translocation of CCN2 is enhanced in bovine embryos are not yet clear, the results of the conducted knockdown experiments in the present study strongly suggest that nuclear CCN2 regulates transcriptional activity in blastomeres during bovine preimplantation development.We previously demonstrated that CCN2 KD affects the expression of TE-expressed genes, and decreases the ratio of TE to ICM cells in bovine embryos, indicating that CCN2 mediates TE development(Akizawa et al, 2018). A recent OCT4 knockout study in bovine embryos revealed that OCT4 is essential for maintaining NANOG expression at the blastocyst stage(Simmet et al, 2018). In the present study, CCN2 KD suppressed both OCT4 and NANOG expression in bovine blastocysts.…”

supporting

confidence: 63%

“…CCN2 is secreted, and generally detected in the Golgi apparatus (Zhou et al, 2008), supporting that it performs important roles in the cytoplasm. However, CCN2 is detected in both cytoplasmic and nuclear fractions in some somatic cells and nuclear-localized CCN2 has been shown to modulate RNA transcription (Wahab, Brinkman, & Mason, 2001 in bovine embryos revealed that OCT4 is essential for maintaining NANOG expression at the blastocyst stage (Simmet et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Significance of CCN2 expression in bovine preimplantation development

Akizawa

Yanagawa

Nagano

et al. 2018

Animal Science Journal

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In mammalian preimplantation development, the first cell lineage segregation occurs during the blastocyst stage, when the inner cell mass and trophectoderm (TE) differentiate. Species-specific analyses are essential to elucidate the molecular mechanisms that underlie this process, since they differ between various species. We previously showed that the reciprocal regulation of CCN2 and TEAD4 is required for proper TE differentiation in bovine blastocysts; however, the function of CCN2 during early embryogenesis has remained otherwise elusive. The present study assessed the spatiotemporal expression dynamics of CCN2 in bovine embryos, and evaluated how changes to CCN2 expression (using a CCN2 knockdown (KD) blastocyst model) regulate the expression of pluripotency-related genes such as OCT4 and NANOG. The conducted quantitative PCR analysis revealed that CCN2 mRNA was expressed in bovine oocytes (at the metaphase stage of their second meiosis) and embryos.Similarly, immunostaining detected both cytoplasmic and nuclear CCN2 at all analyzed oocyte and embryonic stages. Finally, both OCT4 and NANOG expression levels were shown to be significantly reduced in CCN2 KD blastocysts. Together, these results demonstrate that bovine CCN2 exhibits unique expression patterns during preimplantation development, and is required for the proper expression of key regulatory genes in bovine blastocysts. K E Y W O R D Sblastocyst, bovine, CCN2, cell-lineage specification, pluripotency-related genes

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“…To further explore the underlying mechanisms by which KAE alleviates oocyte aging, we examined the expression of embryonic pluripotency-related genes (NANOG, ITGA5, and Oct4) in blastocysts. Previous studies have shown that downregulation of NANOG and Oct4 expression can reduce cell pluripotency (Boyer et al, 2005;Chambers et al, 2003), and that knocking out Oct4 can impair blastocyst development (Simmet et al, 2018). Similarly, NANOG and ITGA5 not only help to maintain embryonic stem cell pluripotency but also promote cell proliferation (Koshida et al, 2005;Morandi et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Kaempferol alleviates the reduction of developmental competence during aging of porcine oocytes

Yao

Jiang

et al. 2019

Animal Science Journal

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Kaempferol (KAE) is a natural flavonoid present in different plant species and exhibits anti‐inflammatory, antioxidant, and anticancer therapeutic properties. In the present study, we investigated the influence and underlying mechanisms of KAE supplementation on porcine oocytes during in vitro aging. The results show that KAE treatment can alleviate the aging‐related reduction of developmental competence. We observed that the blastocyst production rate in aged oocytes treated with 0.1 μM KAE was significantly higher than in untreated aging oocytes (36.78 ± 0.86% vs. 27.55 ± 2.60%, respectively, p < .05). The KAE‐treated aging oocytes had significantly reduced levels of reactive oxygen species (p < .05). Furthermore, the mRNA levels of the embryonic pluripotency‐related genes Oct4, NANOG, and ITGA5 were significantly increased in blastocysts derived from KAE‐treated oocytes (p < .05). During excessive oocyte culture, KAE treatment maintained the mitochondrial membrane potential and reduced apoptosis; however, this was not observed in untreated aging oocytes. In conclusion, our results suggest that KAE treatment can alleviate the aging of porcine oocytes by reducing oxidative stress and improving mitochondrial function.

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OCT4/POU5F1 is required for NANOG expression in bovine blastocysts

Cited by 94 publications

References 46 publications

Beyond the mouse: non-rodent animal models for study of early mammalian development and biomedical research

Beyond the mouse: non-rodent animal models for study of early mammalian development and biomedical research

Significance of CCN2 expression in bovine preimplantation development

Kaempferol alleviates the reduction of developmental competence during aging of porcine oocytes

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