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Abnormalities in human pluripotent cells due to reprogramming mechanisms

Author

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  • Hong Ma

    (Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA
    Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA)

  • Robert Morey

    (University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA)

  • Ryan C. O'Neil

    (Genomic Analysis Laboratory, the Salk Institute for Biological Studies
    Bioinformatics Program, University of California at San Diego)

  • Yupeng He

    (Genomic Analysis Laboratory, the Salk Institute for Biological Studies
    Bioinformatics Program, University of California at San Diego)

  • Brittany Daughtry

    (Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA
    Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA)

  • Matthew D. Schultz

    (Genomic Analysis Laboratory, the Salk Institute for Biological Studies)

  • Manoj Hariharan

    (Genomic Analysis Laboratory, the Salk Institute for Biological Studies)

  • Joseph R. Nery

    (Genomic Analysis Laboratory, the Salk Institute for Biological Studies)

  • Rosa Castanon

    (Genomic Analysis Laboratory, the Salk Institute for Biological Studies)

  • Karen Sabatini

    (University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA)

  • Rathi D. Thiagarajan

    (University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA)

  • Masahito Tachibana

    (Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA
    Present addresses: 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.).)

  • Eunju Kang

    (Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA
    Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA)

  • Rebecca Tippner-Hedges

    (Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA
    Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA)

  • Riffat Ahmed

    (Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA
    Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA)

  • Nuria Marti Gutierrez

    (Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA
    Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA)

  • Crystal Van Dyken

    (Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA
    Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA)

  • Alim Polat

    (Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA
    Present addresses: 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.).)

  • Atsushi Sugawara

    (Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA)

  • Michelle Sparman

    (Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA)

  • Sumita Gokhale

    (University Pathologists LLC, Boston University School of Medicine, Roger Williams Medical Center)

  • Paula Amato

    (Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA)

  • Don P.Wolf

    (Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA)

  • Joseph R. Ecker

    (Genomic Analysis Laboratory, the Salk Institute for Biological Studies
    Howard Hughes Medical Institute, the Salk Institute for Biological Studies)

  • Louise C. Laurent

    (University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA)

  • Shoukhrat Mitalipov

    (Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA
    Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA
    Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA)

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.

Suggested Citation

  • Hong Ma & Robert Morey & Ryan C. O'Neil & Yupeng He & Brittany Daughtry & Matthew D. Schultz & Manoj Hariharan & Joseph R. Nery & Rosa Castanon & Karen Sabatini & Rathi D. Thiagarajan & Masahito Tachi, 2014. "Abnormalities in human pluripotent cells due to reprogramming mechanisms," Nature, Nature, vol. 511(7508), pages 177-183, July.
    • Handle: RePEc:nat:nature:v:511:y:2014:i:7508:d:10.1038_nature13551
    DOI: 10.1038/nature13551
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    Cited by:

    1. Ryoko Araki & Tomo Suga & Yuko Hoki & Kaori Imadome & Misato Sunayama & Satoshi Kamimura & Mayumi Fujita & Masumi Abe, 2024. "iPS cell generation-associated point mutations include many C > T substitutions via different cytosine modification mechanisms," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Maria Arez & Melanie Eckersley-Maslin & Tajda Klobučar & João Gilsa Lopes & Felix Krueger & Annalisa Mupo & Ana Cláudia Raposo & David Oxley & Samantha Mancino & Anne-Valerie Gendrel & Bruno Bernardes, 2022. "Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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