Abstract

The exchange of the oocyte’s genome with the genome of a somatic cell, followed by the derivation of pluripotent stem cells, could enable the generation of specific cells affected in degenerative human diseases. Such cells, carrying the patient’s genome, might be useful for cell replacement. Here we report that the development of human oocytes after genome exchange arrests at late cleavage stages in association with transcriptional abnormalities. In contrast, if the oocyte genome is not removed and the somatic cell genome is merely added, the resultant triploid cells develop to the blastocyst stage. Stem cell lines derived from these blastocysts differentiate into cell types of all three germ layers, and a pluripotent gene expression program is established on the genome derived from the somatic cell. This result demonstrates the feasibility of reprogramming human cells using oocytes and identifies removal of the oocyte genome as the primary cause of developmental failure after genome exchange.

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Data deposits

Illumina array data have been deposited at GEO under accession number GSE28024.

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Acknowledgements

We thank our research subjects for participating. We thank S. Solomon and K. Eggan for discussions and support, L. Bauer for help with blastocyst thawing, D. Kahler for cell sorting, M. Verbitsky and S. Kisselev for microarray hybridization, V. Miljkovic for Affymetrix SNP chip hybridization, C. LeDuc and Y. Ravussin for help with data analysis and mouse work, R. Maehr for DiPS H.1.5, C. Marshall and J. Safran for administrative support, S. Paull for cover art, Z. Hall and S. Chang for critical reading of the manuscript. This research was supported by a UCSD startup fund to K.Z., the New York Stem Cell Foundation primarily, and the Russell Berrie Foundation.

Author information

Affiliations

  1. The New York Stem Cell Foundation Laboratory, New York, New York, USA

    • Scott Noggle
    • , Hector Martinez
    • , Daniel Paull
    • , Sarah Druckenmiller
    •  & Dieter Egli
  2. Department of Bioengineering, University of California at San Diego, La Jolla, California, USA

    • Ho-Lim Fung
    • , Athurva Gore
    •  & Kun Zhang
  3. Center for Women’s Reproductive Care, College of Physicians and Surgeons, Columbia University, New York, New York, USA

    • Kathleen Crumm Satriani
    • , Robert Prosser
    • , Kiboong Oum
    •  & Mark V. Sauer
  4. Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, New York, USA

    • Kathleen Crumm Satriani
    • , Robert Prosser
    • , Kiboong Oum
    •  & Mark V. Sauer
  5. Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, New York, USA

    • Matthew Freeby
    • , Ellen Greenberg
    • , Robin Goland
    •  & Rudolph L. Leibel
  6. Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York, USA

    • Matthew Freeby
    • , Ellen Greenberg
    • , Robin Goland
    •  & Rudolph L. Leibel

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Contributions

R.G. and M.V.S. wrote IRB and consent documents, M.V.S., K.C.S., K.O. and R.P. consented oocyte donors and retrieved oocytes, D.E. and S.N. designed and performed experiments with oocytes, D.E., H.-L.F., A.G., H.M., D.P. and K.Z. characterized stem cell lines, M.F., E.G. and M.V.S. performed skin biopsies, D.E. performed skin cell isolation, soPS and iPS derivation, S.D. performed NYSCF1 derivation, D.E. and R.L.L. wrote the paper with input from all authors. All work with human oocytes and stem cells was performed at the NYSCF laboratory.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Dieter Egli.

Supplementary information

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  1. 1.

    Supplementary Information

    This file contains Supplementary Figures 1-10 with Legends, Supplementary Karyotypes and Fingerprints, Supplementary Tables 1-7, a Supplementary Discussion and Supplementary References.

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DOI

https://doi.org/10.1038/nature10397

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