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

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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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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