Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stem cells (ES cells) from in vitro fertilized embryos (IVF ES cells) represent the ‘gold standard’, they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies.
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Gene Expression Omnibus
Processed data sets can be downloaded from the NCBI GEO under accession GSE53096 for RNA-seq, SNP array and 450K methylation array, and accession GSE57179 for MethylC-seq data. Analysed MethylC-seq data sets can also be accessed at http://neomorph.salk.edu/SCNT/browser.html.
The authors acknowledge the OHSU Embryonic Stem Cell Research Oversight Committee and the Institutional Review Board for providing oversight and guidance. We thank oocyte and sperm donors and the Women’s Health Research Unit staff at the Center for Women’s Health, University Fertility Consultants and the Reproductive Endocrinology and Infertility Division in the Department of Obstetrics and Gynecology of Oregon Health and Science University for their support and procurement of human gametes. We are grateful to C. Penedo for microsatellite analysis and W. Sanger and D. Zaleski for karyotyping services. We are also indebted to Y. Li, H. Sritanaudomchai and D. Melguizo Sanchis for their technical support. We thank the staff at the Institute for Genomic Medicine Genomics Facility at UCSD for running the Infinium HumanMethylation450 BeadChips and sequencing of the RNA-seq libraries. The authors acknowledge the Texas Advanced Computing Center (TACC) at The University of Texas at Austin (http://www.tacc.utexas.edu) and the San Diego Supercomputing Center (through an allocation from the eXtreme Science and Engineering Discovery Environment (XSEDE)) for providing HPC resources that have contributed to the research results reported within this paper. SCNT and iPS cell studies were supported by grants from the Leducq Foundation and OHSU institutional funds. R.M., K.S., R.T. and L.C.L. were supported by the UCSD Department of Reproductive Medicine. Methylome studies were supported by the Salk International Council Chair fund endowment and the Mary K. Chapman Foundation to J.R.E. J.R.E. is an investigator of the Howard Hughes Medical Institute and the Gordon and Betty Moore Foundation (GMBF3034). A.P. received a fellowship from the Swedish Research Council, Vetenskapsrådet. E.K. was partially funded by a fellowship from the Collins Medical Trust.