Stem Cell DNA Has a Unique Chemical Fingerprint
The completed human genome sequence has been metaphorically described as “the book of life.” Expanding upon this metaphor, the map of the epigenetic DNA methylation modifications that adorn the human genome in one cell may be regarded as a single volume in the vast encyclopedia of epigenomes that may be found within the human body. The volume cover depicts a mosaic of an anatomical drawing of a human torso taken from the book “De humani corporis fabrica” (On the Structure of the Human Body) by Andreas Vesalius (1514–1564), who is often regarded as the founder of modern human anatomy. The mosaic is composed of the letter C, which represents the methylcytosine bases identified through shotgun sequencing of bisulfite-converted human genomic DNA, in which only methylated cytosines were not converted to uracil. Together this forms a graphic portrayal of the first comprehensive DNA methylomes of humans, constituting the first two volumes of the potentially vast “Encyclopedia Epigenetica”. Cover image by Ryan Lister. Letter C images: Leo Reynolds, chrisinplymouth, Karyn Christner, Eva Ekeblad (www.flickr.com). Karyotype image: NHGRI Talking Glossary of Genetics.
Stem cells offer enormous potential for repairing damaged tissue but historically they have been hard to obtain. Recent discoveries have shown that normal skin cells can be induced to form stem cells. This provides a readily available source of stem cells, but it’s not known if these “induced” stem cells are really equivalent to embryonic stem cells, or if the range of adult cell types made from them are normal and could be used for therapeutic purposes. An important step to answer these questions is the development of “fingerprints” of all cell types. Chemical modifications to DNA occur in different patterns in each type of cell. These modifications serve as one type of molecular fingerprint that defines what makes a liver cell a liver cell vs. a heart cell vs. a neuron vs. a “pluripotent” stem cell that has the potential to become any one of these cell types and more. To understand how an embryonic stem cell differentiates to become any type of cell in the body, we need to decipher its molecular fingerprint. We also need to know if induced stem cells have the same molecular fingerprint as embryonic stem cells.
Researchers in the Common Fund’s Epigenomics Program have taken the first step toward this goal. They have determined a high resolution fingerprint of one type of chemical group on the DNA of human embryonic stem cells and have compared it to what is found in fibroblasts, a type of cell found in many tissue types, including skin. They found that the fingerprints varied drastically between the two cell types. In addition, an analysis of limited regions of DNA from induced stem cells yielded a partial fingerprint that showed the same characteristics as in human embryonic stem cells. This discovery yields fundamental knowledge about stem cells and indicates that induced stem cells are molecularly similar to embryonic stem cells. It provides a method to identify cells as stem cells, and it is important for future work in which these cells will be used to regenerate adult tissues.
Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009 Nov 19;462(7271):315-22. Epub 2009 Oct 14.PMID: 19829295. Link: http://www.nature.com/nature/journal/v462/n7271/full/nature08514.html
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