Reprogramming after chromosome transfer into mouse blastomeres.
It is well known that oocytes can reprogram differentiated cells, allowing animal cloning by nuclear transfer. We have recently shown that fertilized zygotes retain reprogramming activities, suggesting that such activities might also persist in cleavage-stage embryos. Here, we used chromosome transplantation techniques to investigate whether the blastomeres of two-cell-stage mouse embryos can reprogram more differentiated cells. When chromosomes from one of the two blastomeres were replaced with the chromosomes of an embryonic or CD4(+) T lymphocyte donor cell, we observed nuclear reprogramming and efficient contribution of the manipulated cell to the developing blastocyst. Embryos produced by this method could be used to derive stem cell lines and also developed to term, generating mosaic "cloned" animals. These results demonstrate that blastomeres retain reprogramming activities and support the notion that discarded human preimplantation embryos may be useful recipients for the production of genetically tailored human embryonic stem cell lines.
Egli
Dieter
D
Stowers Medical Institute, Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02140, USA.
Sandler
Vladislav M
VM
Shinohara
Mari L
ML
Cantor
Harvey
H
Eggan
Kevin
K
D000818:Animals; D001757:Blastomeres / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000648:ultrastructure; D019070:Cell Lineage / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics*; D002678:Chimera / Q000235:genetics; D002875:Chromosomes / Q000235:genetics*; D019976:Cloning, Organism / Q000379:methods*; D003571:Cytochalasin B / Q000494:pharmacology; D004624:Embryo Transfer; D053595:Embryonic Stem Cells / Q000378:metabolism; D005456:Fluorescent Dyes / Q000032:analysis; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000032:analysis; D006801:Humans; D008164:Luminescent Proteins / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D009030:Mosaicism / Q000196:embryology; D015739:Nocodazole / Q000494:pharmacology; D035845:Research Embryo Creation / Q000379:methods; D008941:Spindle Apparatus / Q000187:drug effects
D005456:Fluorescent Dyes; D006657:Histones; D008164:Luminescent Proteins; D003571:Cytochalasin B; D015739:Nocodazole
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