title: Abnormalities in human pluripotent cells due to reprogramming mechanisms.
abstract: 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.
authors.affiliation: 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [3].
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.affiliation: 1] Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA [2].
authors.forename: Robert
authors.initials: R
authors.lastname: Morey
authors.affiliation: 1] Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Bioinformatics Program, University of California at San Diego, La Jolla, California 92093, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: O'Neil
authors.affiliation: 1] Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Bioinformatics Program, University of California at San Diego, La Jolla, California 92093, USA.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: He
authors.affiliation: 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Daughtry
authors.affiliation: Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Schultz
authors.affiliation: Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Manoj
authors.initials: M
authors.lastname: Hariharan
authors.affiliation: Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nery
authors.affiliation: Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Castanon
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Sabatini
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA.
authors.forename: Rathi D
authors.initials: RD
authors.lastname: Thiagarajan
authors.affiliation: 1] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [2] Department of Obstetrics and Gynecology, South Miyagi Medical Center, Shibata-gun, Miyagi 989-1253, Japan (M.T.); Department of Cell and Molecular Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden (A.P.).
authors.forename: Masahito
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Eunju
authors.initials: E
authors.lastname: Kang
authors.affiliation: 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tippner-Hedges
authors.affiliation: 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Riffat
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Nuria Marti
authors.initials: NM
authors.lastname: Gutierrez
authors.affiliation: 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Van Dyken
authors.affiliation: 1] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [2] Department of Obstetrics and Gynecology, South Miyagi Medical Center, Shibata-gun, Miyagi 989-1253, Japan (M.T.); Department of Cell and Molecular Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden (A.P.).
authors.forename: Alim
authors.initials: A
authors.lastname: Polat
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugawara
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Sparman
authors.affiliation: University Pathologists LLC, Boston University School of Medicine, Roger Williams Medical Center, Providence, Rhode Island 02118, USA.
authors.forename: Sumita
authors.initials: S
authors.lastname: Gokhale
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Amato
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA.
authors.forename: Don P
authors.initials: DP
authors.lastname: Wolf
authors.affiliation: 1] Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Howard Hughes Medical Institute, the Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Ecker
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Laurent
authors.affiliation: 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [3] Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Shoukhrat
authors.initials: S
authors.lastname: Mitalipov
mesh_terms: D000818:Animals; D002460:Cell Line; D065150:Cellular Reprogramming; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X / Q000235:genetics / Q000378:metabolism; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D055106:Genome-Wide Association Study; D018392:Genomic Imprinting; D006801:Humans; D053652:Nuclear Transfer Techniques / Q000592:standards; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome