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Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer

Nature Genetics volume 38, pages 1323–1328 (2006)Cite this article

Abstract

Since the creation of Dolly via somatic cell nuclear transfer (SCNT)1, more than a dozen species of mammals have been cloned using this technology2. One hypothesis for the limited success of cloning via SCNT (1%–5%)3 is that the clones are likely to be derived from adult stem cells4. Support for this hypothesis comes from the findings that the reproductive cloning efficiency for embryonic stem cells is five to ten times higher than that for somatic cells as donors5,6 and that cloned pups cannot be produced directly from cloned embryos derived from differentiated B and T cells or neuronal cells7,8,9,10. The question remains as to whether SCNT-derived animal clones can be derived from truly differentiated somatic cells. We tested this hypothesis with mouse hematopoietic cells at different differentiation stages: hematopoietic stem cells, progenitor cells and granulocytes. We found that cloning efficiency increases over the differentiation hierarchy, and terminally differentiated postmitotic granulocytes yield cloned pups with the greatest cloning efficiency.

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Figure 1: Different hematopoietic cell subsets used in our nuclear transfer experiments.
Figure 2: Development of cloned embryos reconstructed with purified granulocytes.
Figure 3: Functional characterization of the hematopoietic stem and progenitor cell populations from the BDF1 mice.
Figure 4: Global gene expression profiling analysis of different hematopoietic cells.

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Acknowledgements

We thank M. Watanabe for careful reading and editing of our manuscript. This work was funded by US Department of Agriculture–Agricultural Research Service (USDA-ARS) contract numbers AG 58-1265-2-018 and 58-1265-2-020 as well as the Cooperative State Research, Education, and Extension Service (CSREES)-USDA and the Storrs Agricultural Experiment Station (X.Y. and X.T.), US National Institutes of Health grant HL70561 (T.C.) and the Scholar Award from the American Society of Hematology (T.C.).

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Author notes

  1. Shaorong Gao

    Present address: National Institute of Biological Sciences, Beijing, P.R. China

  2. Hongmei Shen

    Present address: The Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

  3. Kimiko Inoue

    Present address: RIKEN Bioresource Center, Tsukuba, Ibaraki, 305-0074, Japan

  4. Li-Ying Sung and Shaorong Gao: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Regenerative Biology and Department of Animal Science, University of Connecticut, Storrs, 06269, Connecticut, USA

    Li-Ying Sung, Shaorong Gao, Sadie L Smith, Ching-Chien Chang, Kimiko Inoue, X Cindy Tian & Xiangzhong Yang

  2. University of Pittsburgh Cancer Institute and Department of Radiation Oncology, Cancer Stem Cell Program, University of Pittsburgh School of Medicine, Pittsburgh, 15213, Pennsylvania, USA

    Hongmei Shen, Hui Yu, Yifang Song & Tao Cheng

  3. Department of Statistics, University of Connecticut, Storrs, 06269, Connecticut, USA

    Lynn Kuo

  4. Department of Genetics, Yale University School of Medicine, New Haven, 06510, Connecticut, USA

    Jin Lian & Sherman M Weissman

  5. Department of Pathology, Yale University School of Medicine, New Haven, 06510, Connecticut, USA

    Ao Li & David P Tuck

  6. National Institute of Biological Sciences, Beijing, P.R. China

    Hongmei Shen & Kimiko Inoue

  7. The Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Shaorong Gao & Kimiko Inoue

  8. RIKEN Bioresource Center, Tsukuba, Ibaraki, 305-0074, Japan

    Shaorong Gao & Hongmei Shen

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  1. Li-Ying Sung
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Contributions

This study was designed and overseen by X.Y and T.C.; nuclear transfer, characterization of the cloned embryos and data analyses were performed by L.S., S.G., C.C., L.K and X.T; hematopoietic cell isolation and functional assessments were done by H.S., H.Y. and Y.S.; gene expression profiling was performed and analyzed by L.S., S.S., D.T., K.I., J.L, A.L. and S.W.; and T.C., X.Y., S.G. L.S and S.S. contributed to the writing of the paper.

Corresponding authors

Correspondence to Xiangzhong Yang or Tao Cheng.

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The authors declare no competing financial interests.

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Sung, LY., Gao, S., Shen, H. et al. Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer. Nat Genet 38, 1323–1328 (2006). https://doi.org/10.1038/ng1895

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