Letter | Published:

Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells

Nature volume 510, pages 533536 (26 June 2014) | Download Citation



The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells1,2,3, holding promise for autologous cell replacement therapy4,5. Although methods to induce pluripotent stem cells from somatic cells by transcription factors6 are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported7,8,9,10,11, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.

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Gene Expression Omnibus

Data deposits

Microarray data are available at GEO under accession numbers GSE54849 and GSE54876.


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This research was supported the New York Stem Cell Foundation (NYSCF) and a New York State Stem Cell Science (NYSTEM) IIRP Award no. C026184, and the Russell Berrie Foundation Program in Cellular Therapies of Diabetes. We thank S. Mitalipov for helpful discussions and providing reagents, S. Micucci for counting cells in S-phase, and Z. Hall for critical reading of the manuscript. D.E. is a NYSCF-Robertson Investigator.

Author information

Author notes

    • Mitsutoshi Yamada
    •  & Bjarki Johannesson

    These authors contributed equally to this work.


  1. The New York Stem Cell Foundation Research Institute, New York, New York 10032, USA

    • Mitsutoshi Yamada
    • , Bjarki Johannesson
    • , Daniel Paull
    • , Michael W. Nestor
    • , Susan L. Solomon
    •  & Dieter Egli
  2. Stem Cell Unit, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel

    • Ido Sagi
    •  & Nissim Benvenisty
  3. Naomi Berrie Diabetes Center, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA

    • Lisa Cole Burnett
    • , Matthew Freeby
    • , Ellen Greenberg
    • , Robin S. Goland
    •  & Rudolph L. Leibel
  4. Center for Women’s Reproductive Care, College of Physicians and Surgeons, Columbia University, New York 10019, USA

    • Daniel H. Kort
    • , Robert W. Prosser
    •  & Mark V. Sauer
  5. Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York 10032, USA

    • Daniel H. Kort
    • , Robert W. Prosser
    •  & Mark V. Sauer


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M.V.S. supervised the research oocyte donation program and retrieved oocytes. D.E. designed, performed and interpreted nuclear transfer experiments, derived ES cells with M.Y., and wrote the paper with input from all authors. M.Y. performed statistical analysis, M.Y. and B.J. performed stem cell characterization and differentiation, L.C.B. performed neuronal differentiation, I.S. and N.B. performed gene expression analysis, M.W.N. assisted with calcium experiments, D.H.K. performed data analysis, D.P. assisted in nuclear transfer experiments, R.W.P. collected developmental data of IVF embryos, M.F. made the skin biopsy, E.G. coordinated human subjects research, R.S.G. wrote the IRB protocol, R.L.L. contributed project planning, S.L.S. created the environment specifically for this work.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Dieter Egli.

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