Importance of Epigenetic Control
The first question that can be asked is the extent and complexity of the role of epigenetic processes in the determination of cell fate. A clear answer to this question can be seen in the 2011 paper by Lister R, et al. on aberrant epigenomic programming in human induced pluripotent stem cells. As induced pluripotent stem cells (iPSCs) are thought to mimic embryonic stem cells in their pluripotent properties, few epigenetic differences should exist between them. To test this prediction, the authors conducted whole-genome profiling of DNA methylation patterns in several human embryonic stem cell (ESC), iPSC, and progenitor cell lines.
Female adipose cells, lung fibroblasts, and foreskin fibroblasts were reprogrammed into induced pluripotent state with the OCT4, SOX2, KLF4, and MYC genes. Patterns of DNA methylation in ESCs, iPSCs, somatic cells were compared. Lister R, et al. observed significant resemblance in methylation levels between embryonic and induced pluripotent cells. Around 80% of CG dinucleotides in ESCs and iPSCs were methylated, the same was true of only 60% of CG dinucleotides in somatic cells. In addition, somatic cells possessed minimal levels of cytosine methylation in non-CG dinucleotides, while induced pluripotent cells possessed similar levels of methylation as embryonic stem cells, between 0.5 and 1.5%. Thus, consistent with their respective transcriptional activities, DNA methylation patterns, at least on the genomic level, are similar between ESCs and iPSCs.
However, upon examining methylation patterns more closely, the authors discovered 1175 regions of differential CG dinucleotide methylation between at least one ES or iPS cell line. By comparing these regions of differential methylation with regions of cytosine methylation in the original somatic cells, 44-49% of differentially methylated regions reflected methylation patterns of the respective progenitor somatic cells, while 51-56% of these regions were dissimilar to both the progenitor and embryonic cell lines. In vitro-induced differentiation of iPSC lines saw transmission of 88% and 46% of hyper and hypo-methylated differentially methylated regions, respectively.
Two conclusions are readily apparent from this study. First, epigenetic processes are heavily involved in cell fate determination, as seen from the similar levels of cytosine methylation between induced pluripotent and embryonic stem cells, consistent with their respective patterns of transcription. Second, the mechanisms of de-differentiation (and by extension, differentiation) are very complex and cannot be easily duplicated, as seen by the significant number of differentially methylated regions between ES and iPS cell lines. Now that these two points have been established, we can examine some of the epigenetic mechanisms that are thought to regulate cellular differentiation.
Read more about this topic: Cellular Differentiation, Mechanisms, Epigenetic Control of Cellular Differentiation
Famous quotes containing the words importance of, importance and/or control:
“More than ten million women march to work every morning side by side with the men. Steadily the importance of women is gaining not only in the routine tasks of industry but in executive responsibility. I include also the woman who stays at home as the guardian of the welfare of the family. She is a partner in the job and wages. Women constitute a part of our industrial achievement.”
—Herbert Hoover (1874–1964)
“Never before has a generation of parents faced such awesome competition with the mass media for their children’s attention. While parents tout the virtues of premarital virginity, drug-free living, nonviolent resolution of social conflict, or character over physical appearance, their values are daily challenged by television soaps, rock music lyrics, tabloid headlines, and movie scenes extolling the importance of physical appearance and conformity.”
—Marianne E. Neifert (20th century)
“Time in the hand is not control of time,
Nor shattered fragments of an instrument
A proof against the wind; the wind will rise,
We can only close the shutters.”
—Adrienne Rich (b. 1929)