たくさんの種類のソースからiPS細胞をつくっても、最後は収束するっていう話!! 西野さんの渾身の図を貼り付け!! 結構、良い図なんだけど、やはり一般的ではないのかな。
Inducedpluripotent stem cells (iPSCs) could offer a promising alternative forscientists who have found themselves frustrated by the legal and scientific challengesassociated with embryonic stem cell (ESC) research. These cells are derived by expressingselected genes within fully-differentiated adult cells, essentially ‘reprogramming’them into a pluripotent state that closely resembles ESCs.
However, itremains unclear whether the resemblance is strong enough for iPSCs to replaceESCs. For example, chromosomes are chemically marked in ways that stronglyaffect gene expression via so-called ‘epigenetic’ effects; these marks can varydramatically between ESCs and adult cells, but some studies have suggested thatiPSC epigenetic marks may not resemble those from either cell type.
To resolve thisand other questions, a team led by Keio University’s Akihiro Umezawa recently examinedDNA methylation patterns in a diverse array of iPSC lines1. “Epigeneticmodifications such as DNA methylation are considered to be a critical to thereprogramming of iPS cells from somatic cells,” explains lead author KoichiroNishino, a researcher at the University of Miyazaki. “We wanted to know whetherhuman iPSCs generated from various types of cells are dissimilar from eachother, and how continuous cultivation influences the differences between iPSCsand human ESCs.”
Theyexamined 22 human iPSC lines derived from five different cell types, andcompared their DNA methylation patterns relative to the ‘parent’ tissues fromwhich they were generated and five independent ESC lines. Strikingly, the DNAfrom iPSCs exhibited a significantly greater extent of methylation relative toother cells, and the researchers determined that this hypermethylation appearsto occur in a highly dynamic and seemingly unregulated manner in the early aftermathof reprogramming, after the resulting iPSCs have been ‘passaged’ through severalrounds of cell division.
“Theaberrant hypermethylation in iPSCs occurs randomly throughout the genome,” saysNishino. “Even so-called ‘inherited’ methylations, which are considered to havecome from the parental cells, are non-synchronous and stochastic, much like theother aberrant methylations.” Importantly, the methylation process appears tostabilize in subsequent passages, and iPSCs eventually acquire methylationpatterns that closely resemble those observed in ESCs.
Giventhe breadth of the analysis performed by Nishino and Umezawa and colleagues,these results appear to reflect a general characteristic of iPSCs and couldfacilitate future efforts to obtain ESC analogues for regenerative medicineapplications. “iPS cells have to be standardized for clinical use,” saysNishino. “The number of aberrant, differentially-methylated regions could beused as a validation index for iPSC identity.”
1. Nishino, K., Toyoda, M., Yamazaki-Inoue,M., Fukawatase, Y., Chikazawa, E., Sakaguchi, H., Akutsu, H. & Umezawa, A. DNAmethylation dynamics in human induced pluripotent stem cells over time. PLoS Genet. 7, e1002085 (2011).
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