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

Since the creation of Dolly via somatic cell nuclear transfer (SCNT) 1, more than a dozen species of mammals have been cloned using this technology(2). 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 cells(4). 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 donors(5,6) and that cloned pups cannot be produced directly from cloned embryos derived from differentiated B and T cells or neuronal cells(7-10). 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.