title: Comparable frequencies of coding mutations and loss of imprinting in human pluripotent cells derived by nuclear transfer and defined factors.
abstract: The recent finding that reprogrammed human pluripotent stem cells can be derived by nuclear transfer into human oocytes as well as by induced expression of defined factors has revitalized the debate on whether one approach might be advantageous over the other. Here we compare the genetic and epigenetic integrity of human nuclear-transfer embryonic stem cell (NT-ESC) lines and isogenic induced pluripotent stem cell (iPSC) lines, derived from the same somatic cell cultures of fetal, neonatal, and adult origin. The two cell types showed similar genome-wide gene expression and DNA methylation profiles. Importantly, NT-ESCs and iPSCs had comparable numbers of de novo coding mutations, but significantly more than parthenogenetic ESCs. As iPSCs, NT-ESCs displayed clone- and gene-specific aberrations in DNA methylation and allele-specific expression of imprinted genes. The occurrence of these genetic and epigenetic defects in both NT-ESCs and iPSCs suggests that they are inherent to reprogramming, regardless of derivation approach.
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA.
authors.forename: Bjarki
authors.initials: B
authors.lastname: Johannesson
authors.affiliation: Stem Cell Unit, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Sagi
authors.affiliation: Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Athurva
authors.initials: A
authors.lastname: Gore
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Paull
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Stem Cell Unit, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Golan-Lev
authors.affiliation: Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: Naomi Berrie Diabetes Center & Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: LeDuc
authors.affiliation: Departments of Systems Biology and Biomedical Informatics, JP Sulzberger Columbia Genome Center, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Shen
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Stern
authors.affiliation: Department of Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Nanfang
authors.initials: N
authors.lastname: Xu
authors.affiliation: Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.affiliation: Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Eunju
authors.initials: E
authors.lastname: Kang
authors.affiliation: Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Shoukhrat
authors.initials: S
authors.lastname: Mitalipov
authors.affiliation: Center for Women's Reproductive Care, College of Physicians and Surgeons, Columbia University, New York, NY 10019, USA.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Sauer
authors.affiliation: Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Stem Cell Unit, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel. Electronic address: nissimb@cc.huji.ac.il.
authors.forename: Nissim
authors.initials: N
authors.lastname: Benvenisty
authors.affiliation: The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA; Naomi Berrie Diabetes Center & Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: d.egli@nyscf.org.
authors.forename: Dieter
authors.initials: D
authors.lastname: Egli
mesh_terms: D000328:Adult; D001483:Base Sequence; D002999:Clone Cells; D019175:DNA Methylation / Q000235:genetics; D005786:Gene Expression Regulation; D056426:Genetic Loci; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D059645:Mutation Rate; D053652:Nuclear Transfer Techniques; D016366:Open Reading Frames / Q000235:genetics*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism