Discredited Stem Cells Created by Virgin Birth

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In 2004, Korean investigators lead by Woo Suk Hwang at Seoul National University announced the creation of the world’s first human embryonic stem cell line generated by somatic cell nuclear transfer (SCNT), which involves the transfer of DNA, usually from a skin cell, into an egg cell that has had its DNA-containing nucleus removed. The work, published in the prominent journal Science, was retracted in 2006 amidst evidence that the researchers had falsified their data.

However, a study published online August 2nd, 2007, by the journal Cell Stem Cell reports that the Koreans unintentionally created the world’s first human embryonic stem cell derived by parthenogenesis, or virgin birth. Development is triggered spontaneously from the egg alone without the need for sperm fertilization.

Parthenogenesis is a natural phenomena that occurs in some insects, including aphids, honeybees and formicine ants, as well as some reptiles, including geckos, rock lizards and Komodo dragons. The process also occurs, though more rarely, in plants. There are no known cases of naturally occurring parthenogenesis in mammals because of imprinted genes. Imprinted genes are genes whose expression is determined by the parent that contributed them instead of following the usual rule of inheritance in which both copies of an inherited gene (one from the mother and one from the father) are equally expressed. In 1899, Jacques Loeb documented the first case of artificial parthenogenesis, treating sea urchin eggs with inorganic salt solutions to initiate embryonic development instead of the sperm of the male urchin [1].

In January 2007, researchers from the Harvard Stem Cell Institute analyzed patterns of genetic recombination in parthenogenetically derived mouse embryonic stem (ES) cell lines [2]. What they found was surprising: in contrast to ES cells produced by nuclear transfer, which are homozygous at most loci (meaning they contain two copies of the same form of a given gene at a specific location on a chromosome, referred to as an allele), parthenogenetically derived ES cells show predominant heterozygosity (meaning they have different alleles at a number of chromosomal locations) as a result of meiotic recombination. Meiosis is the process of cell division in sexually reproducing organisms that results in a reduction in the number of chromosomes in reproductive cells and leads to the production of gametes in animals (male gametes are sperm and female gametes are eggs) and spores in plants. Meiotic recombination, also known as crossing over, is a process of physical rearrangement occurring between two strands of DNA. A common event during meiosis, recombination leads to offspring that has different combinations of genes from their parents.

Researchers examined Hwang’s cell line using genome-wide single nucleotide polymorphism (SNP) analysis and found recombination patterns that are consistent with its derivation from a parthenogenetically derived embryo. SNP (pronounced “snip”) analysis identifies DNA sequence variations that occur when a single nucleotide – A, T, C, or G – in the genome is changed, producing different alleles. Common SNPs only have two alleles. For example, ATCGATCG and ATCAATCG represent two alleles: G and A. SNPs make up about 90% of all human genetic variation and occur every 100 to 300 bases along the 3-billion-base human genome [3]. These small variations in DNA sequence can have a significant impact on how individuals respond to disease, drugs and other therapies.

Parthenogenesis may provide a method for the generation of stem cells that are therapeutically valuable for women. Stem cells created by parthenogenesis don’t require cloning and won’t be rejected by the host immune system. However, concerns regarding safety and differentaion efficiency exist, as mouse parthenogenetic embryos are unable to complete full development due to the absense of paternally expressed imprinted genes, and tissues derived from parthenogenetic embryonic stem cells appear to have growth defects [4]. Further study is required to characterize the stem cells generated in the study. Nevertheless, parthenogenetically derived stem cells are another step closer to patient-specific, personalized medicine.

References

1. Jacques Loeb. On the nature of the process of fertilization and the artificial production of normal larvae (plutei) from the unfertilized eggs of the sea urchin. Am J Physiol 1899 3:135-138. Reprinted in Studies in General Physiology. Chicago: The University of Chicago Press, 1905. pp. 539-543.
2. Kim et al. Histocompatible embryonic stem cells by parthenogenesis. Science 2007 315, 482-486.
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3. SNP Fact Sheet. Human Genome Project Information.
4. Hernandez et al. Paternal and maternal genomes confer opposite effects on proliferation, cell-cycle length, senescence, and tumor formation. Proc. Natl. Acad. Sci. U. S. A. 2003 100, 13344-13349.
   View abstract