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Reprogramming efficiency following somatic cell nuclear transfer is influenced by the differentiation and methylation state of the donor nucleus.

TitleReprogramming efficiency following somatic cell nuclear transfer is influenced by the differentiation and methylation state of the donor nucleus.
Publication TypeJournal Article
Year of Publication2006
AuthorsBlelloch R, Wang Z, Meissner A, Pollard SM, Smith A, Jaenisch R
JournalStem Cells
Volume24
Issue9
Pagination2007-13
Date Published2006 Sep
ISSN1066-5099
KeywordsAnimals, Cell Differentiation, Cell Nucleus, Cells, Cultured, DNA (Cytosine-5-)-Methyltransferase, DNA Methylation, DNA-Binding Proteins, Female, Fibroblasts, Gene Expression Regulation, Developmental, Homeodomain Proteins, Mice, Mice, Inbred C57BL, Neurons, Octamer Transcription Factor-3, Pluripotent Stem Cells, Promoter Regions, Genetic, Research Embryo Creation, RNA, Messenger, Sequence Analysis, DNA
Abstract

Reprogramming of a differentiated cell nucleus by somatic cell nuclear transplantation is an inefficient process. Following nuclear transfer, the donor nucleus often fails to express early embryonic genes and establish a normal embryonic pattern of chromatin modifications. These defects correlate with the low number of cloned embryos able to produce embryonic stem cells or develop into adult animals. Here, we show that the differentiation and methylation state of the donor cell influence the efficiency of genomic reprogramming. First, neural stem cells, when used as donors for nuclear transplantation, produce embryonic stem cells at a higher efficiency than blastocysts derived from terminally differentiated neuronal donor cells, demonstrating a correlation between the state of differentiation and cloning efficiency. Second, using a hypomorphic allele of DNA methyltransferase-1, we found that global hypomethylation of a differentiated cell genome improved cloning efficiency. Our results provide functional evidence that the differentiation and epigenetic state of the donor nucleus influences reprogramming efficiency.

DOI10.1634/stemcells.2006-0050
Alternate JournalStem Cells
PubMed ID16709876
PubMed Central IDPMC3000431
Grant ListG0300058 / / Medical Research Council / United Kingdom
G0800784 / / Medical Research Council / United Kingdom
G9806702 / / Medical Research Council / United Kingdom
K08 NS048118 / NS / NINDS NIH HHS / United States
K08 NS048118-01A1 / NS / NINDS NIH HHS / United States
K08 NS48118 / NS / NINDS NIH HHS / United States
R01 HD045022 / HD / NICHD NIH HHS / United States
R37 CA84198-04 / CA / NCI NIH HHS / United States
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