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This phenomenon could affect stem cell-based models of diseasescaused by mutations of the X chromosome, such as Lesch-Nyhandisease, the researchers note. These cell-based models require thatonly the diseased copy of an X-linked gene be expressed, with thenormal copy of the gene in females silenced via XCI. As theoriginally inactive X chromosome becomes active, the normal copy ofthe gene is expressed, changing the phenotype of the cells fromdiseased to normal. "If an X chromosome that was assumed to be inactive is actuallyactive, scientists may find that their cells perplexingly changefrom mutant to normal over time in culture," Loring said. Another epigenomic aberration noted in pluripotent cells was inimprinted genes. Human cells contain two copies of most genes: oneinherited from the mother and one from the father. In most cases,both the maternal and paternal copies of a gene are expressedequally. This is not the case, however, for imprinted genes, someof which are only expressed from the paternal chromosomes andothers expressed only from the maternal chromosomes. Thisparent-of-origin specific gene expression involves silencing of oneof the copies of the gene. Abnormalities in this selectivesilencing of genes can lead to serious developmental diseases. The study found that, while the patterns of DNA methylationrequired to maintain imprinted gene silencing were stable in all ofthe somatic tissues, surprisingly, frequent aberrations in thepatterns of DNA methylation existed in imprinted genes in the stemcells. Some of these aberrations arose very early in theestablishment of the cell lines, while others crept in with thepassage of time. Interestingly, the team was able to link at least some of theseaberrations to the conditions under which the stem cells werecultured in the lab. This suggests that researchers who use stemcells to study diseases linked to genomic imprinting will need touse conditions that best maintain imprinted gene silencing. The researchers found another surprise - this one having to do withthe basic process by which stem cells become specialized adultcells. Scientists have assumed that most genes are active at theearliest stages of human development, and that unnecessary ones areswitched off as the cells developed specialized functions. "For example, during the process of differentiation from a stemcell into a neuron, you might expect to observe silencing of allthe genes that are important for the kidney, the pancreas, and theliver," said Kristopher Nazor, a Scripps Research Kellogg School ofScience and Technology graduate student who is lead author of thestudy. "But we found something quite different." When the team compared stem cells with adult cells taken fromtissue samples, rather than seeing mostly active genes in the stemcells and selectively silenced genes in the adult ones, they sawthe opposite: in the stem cells, the researchers found that geneslinked to the development of specialized tissue cells were silentand methylated, while in the adult cells regions of DNA involved incell type specification were active and unmethylated. Thescientists could reproduce some aspects of the developmentalchanges in culture: when stem cells were differentiated into neuralcells in the culture dish, the patterns of DNA methylation becamesimilar to those seen in human brain tissue. This implies that, contrary to conventional wisdom, the genesresponsible for transforming stem cells into tissue cells wereinitially silent, and were switched on during the process ofdifferentiation. Additional References Citations. I am an expert from magnesiumferrosilicon.com, while we provides the quality product, such as Metal Inoculation Manufacturer , FeSiMg Alloy Manufacturer, Ferro Silicon Barium,and more.
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