Author(s): Li-Ying Sung1, 6, Shaorong Gao1, 6, Hongmei Shen2, Hui Yu2, Yifang Song2, Sadie L Smith1, Ching-Chien Chang1, Kimiko Inoue1, Lynn Kuo3, Jin Lian4, Ao Li5, X Cindy Tian1, David P Tuck5, Sherman M Weissman4, Xiangzhong Yang1 & Tao Cheng2

1-Center for Regenerative Biology and Department of Animal Science, University of Connecticut, Storrs, Connecticut 06269, USA.
2-Cancer Stem Cell Program, University of Pittsburgh Cancer Institute and Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
3-Department of Statistics, University of Connecticut, Storrs, Connecticut 06269, USA.
4-Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
5-Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
6-These authors contributed equally to this work.

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

Summary: 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.

Source: Nature Genetics – 38, 1323 – 1328 (2006)