Can a genetic signature identify the origin of a human stem cell line? Scientists report that a widely available method for comprehensive genetic analysis can help distinguish the type of human embryo that stem cells come from. The research, to be published online August 2nd by the journal Cell Stem Cell, published by Cell Press, also provides an intriguing new insight into the largest scandal in the history of human stem cell research.
Different methods can be used to make embryonic stem (ES) cells. Human ES cells are typically made from embryos that are donated by couples that have undergone in vitro fertilization as a form of assisted reproduction therapy for infertility. Parthenogenetic ES (pES) cells are derived from embryos created by artificial activation of eggs in the absence of sperm. ES cells generated by somatic nuclear transfer (ntES) are derived from embryos that are created when the nucleus of an egg is replaced by the nucleus from a body cell. Creation of human ntES are pES are of particular interest to researchers as they may provide stem cells that are nearly genetically identical to the donor and, therefore, particularly well suited for customized, rejection-proof cell transplantation therapies.
To better understand the specific genetic recombination events that occur in ES cells derived by these different methods, researchers under the direction of Dr. George Q. Daley of Children's Hospital Boston and the Harvard Stem Cell Institute together with an international set of collaborators completed a thorough genome-wide analysis of five novel pES cells, 30 mouse ntES, as well as the SCNT-hES-1 cell line, the first human ES cell line purportedly generated by Korean scientists using human eggs and somatic cell nuclear transfer. The original paper describing the SCNT-hES-1 cell line was retracted after an investigation by the Seoul National University revealed research misconduct, but the derivation of the cell line was never fully resolved.
The study found that ntES and pES cells have distinct DNA recombination signatures. Those made from parthenogenetic embryos display a telltale genetic pattern close to the center of chromosomes. The results also revealed that the SCNT-hES-1 cell line was not derived by somatic nuclear transfer as was previously claimed. "Our analysis shows that the recombination pattern of SCNT-hES-1 is distinct from that of an ntES line and is consistent with its derivation from a parthenogenetic embryo. Thus, we conclude that the derivation of SCNT-hES-1 represented the first successful isolation of human pES cells," offers Dr. Daley.
The authors conclude that, although there are still significant obstacles to overcome in the generation of pES cells, parthenogenesis is an efficient way of generating embryos and that it may someday be feasible to generate patient-specific pES cells from females. "If careful genetic and functional analysis of tissues derived from human pES cells show them to be safe and effective, then pES cells might represent a favorable source for tissue replacement therapies," says Dr. Daley.
The researchers include Kitai Kim, Kitwa Ng, and George Q. Daley of Children's Hospital Boston, Dana Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Stem Cell Institute in Boston; Peter J. Rugg-Gunn of University of Cambridge and The Hospital for Sick Children in Toronto; Jae-Hung Shieh and Malcolm A. Moore of Memorial Sloan-Kettering Cancer Center in New York; Oktay Kirak and Rudolf Jaenisch of Whitehead Institute for Biomedical Research in Cambridge; Teruhiko Wakayama of RIKEN Kobe in Kobe; Roger A. Pedersen of The Hospital for Sick Children in Toronto. This study was supported by grants from the NIH and the NIH Director's Pioneer Award of the NIH Roadmap for Medical Research, and by private philanthropic funds received by the Harvard Stem Cell Institute and Children's Hospital Boston.