RRC ID |
5284
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著者 |
Inoue K, Noda S, Ogonuki N, Miki H, Inoue S, Katayama K, Mekada K, Miyoshi H, Ogura A.
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タイトル |
Differential developmental ability of embryos cloned from tissue-specific stem cells.
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ジャーナル |
Stem Cells
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Abstract |
Although cloning animals by somatic cell nuclear transfer is generally inefficient, the use of certain nuclear donor cell types may significantly improve or deteriorate outcomes. We evaluated whether two multipotent stem cell lines produced in vitro--neural stem cells (NSCs) and mesenchymal stem cells (MSCs)--could serve as nuclear donors for nuclear transfer cloning. Most (76%) NSC-derived embryos survived the two-cell-to-four-cell transition, the stage when the major zygotic gene activation occurs. Consistent with this observation, the expression patterns of zygotically active genes were better in NSC-derived embryos than in fibroblast clone embryos, which arrested at the two-cell stage more frequently. Embryo transfer experiments demonstrated that at least some of these NSC embryos had the ability to develop to term fetuses (1.6%, 3/189). In contrast, embryos reconstructed using MSCs showed a low rate of in vitro development and never underwent implantation in vivo. Chromosomal analysis of the donor MSCs revealed very frequent aneuploidy, which probably impaired the potential for development of their derived clones. This is the first demonstration that tissue-specific multipotent stem cells produced in vitro can serve as donors of nuclei for cloning mice; however, these cells may be prone to chromosomal aberrations, leading to high embryonic death rates. We found previously that hematopoietic stem cells (HSCs) are very inefficient donor cells because of their failure to activate the genes essential for embryonic development. Taken together, our data led us to conclude that tissue-specific stem cells in mice, namely NSCs, MSCs, and HSCs, exhibited marked variations in the ability to produce cloned offspring and that this ability varies according to both the epigenetic and genetic status of the original genomes. Disclosure of potential conflicts of interest is found at the end of this article.
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巻・号 |
25(5)
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ページ |
1279-85
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公開日 |
2007-5-1
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DOI |
10.1634/stemcells.2006-0747
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PII |
2006-0747
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PMID |
17255518
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MeSH |
Animals
Cell Differentiation
Chromosomes, Mammalian / genetics
Cytogenetics
Embryo, Mammalian / embryology*
Female
Gene Expression Regulation, Developmental
Genes, Developmental
Humans
Male
Mesenchymal Stem Cells / cytology*
Mice
Mice, Inbred C57BL
Neurons
Nuclear Transfer Techniques
Organ Specificity
Pluripotent Stem Cells / cytology*
Research Embryo Creation*
Transcriptional Activation
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IF |
6.022
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引用数 |
45
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WOS 分野
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BIOTECHNOLOGY & APPLIED MICROBIOLOGY
HEMATOLOGY
ONCOLOGY
CELL & TISSUE ENGINEERING
CELL BIOLOGY
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リソース情報 |
実験動物マウス |
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