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<\/p>\n\nJoseph R. Ecker, Professor – Genomic Analysis Laboratory\n <\/p>\n
Haga clic aqu\u00ed<\/a> for a high resolution image.<\/p>\n \nImagen: Cortes\u00eda del Instituto Salk de Estudios Biol\u00f3gicos\n<\/p>\n<\/div>\n \nThe researchers discovered that stem cells created by moving genetic material from a skin cell into an empty egg cell\u2014rather than coaxing adult cells back to their embryonic state by artificially turning on a small number of genes\u2014more closely resemble human embryonic stem cells, which are considered the gold standard in the field.\n<\/p>\n \n\t“These cells created using eggs’ cytoplasm have fewer reprogramming issues, fewer alterations in gene expression levels and are closer to real embryonic stem cells,” says co-senior author Joseph R. Ecker<\/a>, professor and director of Salk’s Genomic Analysis Laboratory and co-director of the Center of Excellence for Stem Cell Genomics. The results of the study were published today in Naturaleza<\/em><\/a>.\n\t<\/p>\n \n\tHuman embryonic stem cells (hESCs) are directly pulled from unused embryos discarded from in-vitro fertilization, but ethical and logistical quandaries have restricted their access. In the United States, federal funds have limited the use of hESCs so researchers have turned to other methods to create stem cells. Most commonly, scientists create induced pluripotent stem (iPS) cells by starting with adult cells (often from the skin) and adding a mixture of genes that, when expressed, regress the cells to a pluripotent stem-cell state. Researchers can then coax the new stem cells to develop into cells that resemble those in the brain or in the heart, giving scientists a valuable model for studying human disease in the lab.\n\t<\/p>\n \n\tOver the past year, a team at OHSU built upon a technique called somatic cell nuclear transfer (the same that is used for cloning an organism, such as Dolly the sheep) to transplant the DNA-containing nucleus of a skin cell into an empty human egg, which then naturally matures into a group of stem cells.\n\t<\/p>\n \n\tEcker, holder of the Presidente del Consejo Internacional Salk de Gen\u00e9tica<\/a>, teamed up with Shoukhrat Mitalipov, developer of the new technique and director of the Center for Embryonic Cell and Gene Therapy<\/a> at OHSU, and UCSD assistant professor Louise Laurent to carry out the first direct comparison of the two approaches. The scientists created four lines of nuclear transfer stem cells all using eggs from a single donor, along with seven lines of iPS cells and two lines of the gold standard hESCs. All cell lines were shown to be able to develop into multiple cell types and had nearly identical DNA content contained within them.\n\t<\/p>\n \nBut when they looked closer at the cells, the researchers spotted some differences: the patterns of methylation\u2014chemical flags that are added to genes to control their expression\u2014varied between the cell lines. This indicates a difference in how and when genes, despite having identical sequences, might be expressed. The methylation of nuclear transfer cells more closely resembled hESCs than the iPS cells did. And when the investigators looked at patterns of actual gene expression\u2014by measuring the levels of particular RNA strands produced by each cell\u2014the differences continued. Once again, nuclear transfer cells had RNA levels closer to embryonic cells, making them more accurate for basic research and therapeutic studies. <\/p>\n “Both the DNA methylation and gene expression data show that nuclear transfer does a better job at erasing the signature of the original skin cell,” says Laurent, who is a co-senior author of the paper.<\/p>\n “If you believe that gene expression is important, which we do, then the closer you get to the gene expression patterns of embryonic stem cells, the better,” Ecker says. “Right now, nuclear transfer cells look closer to the embryonic stem cells than do the iPS cells.”<\/p>\n \nEcker doesn’t expect labs to race to make the switch to nuclear transfer protocols\u2014after all, the method falls within those restricted for federal funding. But he thinks the new observation likely holds lessons that could help improve the protocols for making iPS cells.\n<\/p>\n \n“What this is telling us is that you can use the standard mix of genes and they do a pretty good job of creating iPS cells,” Ecker says. “But they’re not perfect. The material in an egg does a better job than just those four genes alone.”\n<\/p>\n \nIf researchers can pin down what it is within an egg that drives the production of pluripotent stem cells, they may be able to integrate that knowledge into iPS methods to improve stem cell therapy for disease.\n<\/p>\n \n“At this point, nuclear transfer stem cells combine the key advantages of both hESCs and iPS cells and, as such, are ideal for clinical applications in regenerative therapy,” adds Mitalipov.\n<\/p>\n \tOther researchers on the study were Ryan C. O’Neil, Yupeng He, Matthew D. Schultz, Manoj Hariharan, Joseph R. Nery, and Rosa Castanon of the Instituto Salk de Estudios Biol\u00f3gicos<\/a>; Hong Ma, Brittany Daughtry, Masahito Tachibana, Eunju Kang, Rebecca Tippner-Hedges, Riffat Ahmed, Nuria Marti Gutierrez, Crystal Van Dyken, Alimujiang Fulati, Atsushi Sugawara, Michelle Sparman, Paula Amato and Don P. Wolf of Oregon Health & Science University<\/a>; Robert Morey, Karen Sabatini and Rathi D. Thiagarajan of the University of California, San Diego; and Sumita Gokhale of the Boston University School of Medicine<\/a>.\n\t<\/p>\n \n\tJoseph R. Ecker is an Investigator of the Howard Hughes Medical Institute<\/a> y Gordon and Betty Moore Foundation<\/a>. Additionally, the work and researchers involved were supported by grants from the Leducq Foundation<\/a>; Oregon Health & Science University<\/a>; the University of California San Diego Department of Reproductive Medicine<\/a>; the Salk International Council Chair fund endowment; the Mary K. Chapman Foundation<\/a>; the Swedish Research Council<\/a>; and the Collins Medical Trust<\/a>.\n<\/p>\n Acerca del Instituto Salk de Estudios Biol\u00f3gicos:<\/strong> Los logros del cuerpo docente han sido reconocidos con numerosos galardones, entre los que se incluyen premios Nobel y la pertenencia a la Academia Nacional de Ciencias. Fundado en 1960 por el Dr. Jonas Salk, pionero en la vacuna contra la poliomielitis, el Instituto es una organizaci\u00f3n independiente sin fines de lucro y un hito arquitect\u00f3nico.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[42],"disease-research":[146],"class_list":["post-2489","disclosure","type-disclosure","status-publish","hentry","faculty-joseph-ecker","disease-research-aging-and-regenerative-medicine"],"acf":[],"yoast_head":"\n
\nThe Salk Institute for Biological Studies is one of the world’s preeminent basic research institutions, where internationally renowned faculty probes fundamental life science questions in a unique, collaborative and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer’s, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.<\/p>\n