Publications (4)46.67 Total impact
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Article: Production of mouse embryonic stem cell lines from maturing oocytes by direct conversion of meiosis into mitosis.
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ABSTRACT: ESCs are most commonly derived from embryos originating from oocytes that reached metaphase II. We describe here a novel approach where ESCs with all pluripotency parameters were established from oocytes in which metaphase I was converted, from the cell cycle perspective, directly into metaphase II-like stage without the intervening anaphase to telophase I transition. The resulting embryos initiate development and reach the blastocyst stage from which the ESC lines are then established. Thus, our approach could represent an ethically acceptable method that can exploit oocytes that are typically discarded in in vitro fertilization clinics. Moreover, our results also indicate that the meiotic cell cycle can be converted into mitosis by modulating chromosomal contacts that are typical for meiosis with subsequent licensing of chromatin for DNA replication.Stem Cells 03/2011; 29(3):517-27. · 7.78 Impact Factor -
Article: BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture conditions on laminin.
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ABSTRACT: Because mouse embryonic stem cells (mESCs) do not contribute to the formation of extraembryonic placenta when they are injected into blastocysts, it is believed that mESCs do not differentiate into trophoblast whereas human embryonic stem cells (hESCs) can express trophoblast markers when exposed to bone morphogenetic protein 4 (BMP4) in vitro. To test whether mESCs have the potential to differentiate into trophoblast, we assessed the effect of BMP4 on mESCs in a defined monolayer culture condition. The expression of trophoblast-specific transcription factors such as Cdx2, Dlx3, Esx1, Gata3, Hand1, Mash2, and Plx1 was specifically upregulated in the BMP4-treated differentiated cells, and these cells expressed trophoblast markers. These results suggest that BMP4 treatment in defined culture conditions enabled mESCs to differentiate into trophoblast. This differentiation was inhibited by serum or leukemia inhibitory factor, which are generally used for mESC culture. In addition, we studied the mechanism underlying BMP4-directed mESC differentiation into trophoblast. Our results showed that BMP4 activates the Smad pathway in mESCs inducing Cdx2 expression, which plays a crucial role in trophoblast differentiation, through the binding of Smad protein to the Cdx2 genomic enhancer sequence. Our findings imply that there is a common molecular mechanism underlying hESC and mESC differentiation into trophoblast.In Vitro Cellular & Developmental Biology - Animal 05/2010; 46(5):416-30. · 1.31 Impact Factor -
Article: Stable embryonic stem cell lines in rabbits: potential small animal models for human research.
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ABSTRACT: Although embryonic stem (ES) cell lines derived from mice and primates are used extensively, the development of such lines from other mammals is extremely difficult because of their rapid decline in proliferation potential and pluripotency after several passages. This study describes the establishment of rabbit ES cell lines with indefinite proliferation potential. It was found that the feeder cell density determines the fate of rabbit ES cells, and that maximum proliferation potential was obtained when they were cultured on a feeder cell density of one-sixth of the density at confluency. Higher and lower densities of feeder cells induced ES cell differentiation or division arrest. Under optimized conditions, rabbit ES cells were passaged 50 times, after which they still possessed high telomerase activity. This culture system enabled efficient gene transduction and clonal expansion from single cells. During culture, rabbit ES cells exhibited flattened monolayer cell colonies, as reported for monkey and human ES cells, and expressed pluripotency markers. Embryoid bodies and teratomas formed readily in vitro and in vivo respectively. These ES cell lines can be safely cryopreserved for later use. Thus, rabbit ES cells can be added to the list of stable mammalian ES cells, enabling the rabbit to be used as a small animal model for the study of human cell transplantation therapy.Reproductive biomedicine online 12/2008; 17(5):706-15. · 2.04 Impact Factor -
Article: Role of retrotransposon-derived imprinted gene, Rtl1, in the feto-maternal interface of mouse placenta.
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ABSTRACT: Eutherian placenta, an organ that emerged in the course of mammalian evolution, provides essential architecture, the so-called feto-maternal interface, for fetal development by exchanging nutrition, gas and waste between fetal and maternal blood. Functional defects of the placenta cause several developmental disorders, such as intrauterine growth retardation in humans and mice. A series of new inventions and/or adaptations must have been necessary to form and maintain eutherian chorioallantoic placenta, which consists of capillary endothelial cells and a surrounding trophoblast cell layer(s). Although many placental genes have been identified, it remains unknown how the feto-maternal interface is formed and maintained during development, and how this novel design evolved. Here we demonstrate that retrotransposon-derived Rtl1 (retrotransposon-like 1), also known as Peg11 (paternally expressed 11), is essential for maintenance of the fetal capillaries, and that both its loss and its overproduction cause late-fetal and/or neonatal lethality in mice.Nature Genetics 03/2008; 40(2):243-8. · 35.53 Impact Factor
