Cloned Human Embryos Successfully Reprogrammed Using Human Eggs
News Feb 05, 2009
Advanced Cell Technology, Inc. and its collaborators reported today that human oocytes (or ‘eggs’) have the capacity to extensively reprogram adult human cells.
The research, which appears online ahead of print in the journal Cloning and Stem Cells, demonstrates that although human-to-human clones and human-to-animal clones appear similar, the pattern of reprogramming of the donor human cell is dramatically different.
In contrast to the human-animal hybrids, the gene expression pattern of the human clones was highly similar to normal human embryos. The paper is available free online at www.liebertpub.com/clo.
Since the cloning of Dolly the Sheep over a decade ago, somatic cell nuclear transfer (SCNT) has been considered a promising way to generate personalized stem cells to repair the body without fear of tissue rejection. Due to the serious shortage of human donor eggs, cows, rabbits, and other animals have long been considered an attractive surrogate source of eggs.
Although previous reports have documented the formation of cloned embryos using both human and animal eggs, to-date, there has been no data indicating whether –and to what extent - the donor DNA was reprogrammed.
This new study looked at the reprogramming of human cells using eggs obtained from human and animal sources, and shows for the first time that the donor DNA in the cloned human embryos is extensively reprogrammed through extensive up-regulation (‘turning on’ of genes) with similar expression patterns to normal human embryos. Nearly all of the key differentially-expressed genes were activated in the human clones. In distinct contrast, the majority of these genes were down-regulated or silenced in the human-animal hybrids.
“We examined the factors recently used to reprogram skin cells (to induce pluripotent stem cells),” said Robert Lanza, MD, Chief Scientific Officer at ACT, and senior author of the study.
“At the center of cellular reprogramming lies the activation of the transcription factors Oct4, Sox2, and nanog. These core factors were activated in both the normal and cloned human embryos. In striking contrast, the human-animal hybrids showed no difference or a down-regulation of these critical pluripotency genes - effectively silencing them-thus making the generation of stem cells impossible. Without appropriate reprogramming, these data call into question the potential use of animal egg sources to generate patient-specific stem cells. It also renders the moral controversy surrounding the use of human-animal hybrids mute.”
Previous studies have confirmed the ability of animal eggs to support interspecies cell division to the embryo stage, and in a few closely-related bovid species, successful development to term. However, there are clear differences in compatibility. Distantly-related animal combinations generally arrest at the cleavage-stage, although there have been reports of blastocyst formation. Our group and others have successfully used eggs to clone closely-related species.