Open AccessReprogramming Efficiency Following Somatic Cell Nuclear Transfer Is Influenced by the Differentiation and Methylation State of the Donor Nucleus
Author(s) -
Blelloch Robert,
Wang Zhongde,
Meissner Alex,
Pollard Steven,
Smith Austin,
Jaenisch Rudolf
Publication year - 2006
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2006-0050
Subject(s) - biology , reprogramming , embryonic stem cell , somatic cell , cellular differentiation , somatic cell nuclear transfer , stem cell , microbiology and biotechnology , chromatin , epigenetics , dna methylation , cell potency , cloning (programming) , transplantation , genetics , adult stem cell , cell , embryo , embryogenesis , gene , gene expression , blastocyst , medicine , computer science , programming language , surgery
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.