DNA methylation dynamics in human induced pluripotent stem cells

Tlexander

DNA methylation dynamics in human induced pluripotent stem cells+ e' d" g+ Z: t2 ^) ]. F

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Abstract Indeed human induced pluripotent stem cells0 t% ~) _$ w- W/ L; L& c6 m
(hiPSCs) are considered to be powerful tools in regenerative
" p& S+ r9 {0 z, B# q( v8 ]medicine. To enable the use of hiPSCs in the field of4 n; _5 ?! B2 y  @7 j# a+ f: s5 h
regenerative medicine, it is necessary to understand the" R2 d/ Q3 a# ?$ {- m' W; J$ y( w8 I
mechanisms of reprogramming during the transformation$ z8 r) c2 ]( D: L; E' x
of somatic cells into hiPSCs. Genome-wide epigenetic/ E2 d, {. h/ g0 [  ]
modification constitutes a critical event in the generation of/ v+ l& w7 X3 F; Z
iPSCs. In other words, to analyze epigenetic changes in  b2 x9 [0 {2 l% \* f
iPSCs means to elucidate reprogramming processes. We
4 K, D% o4 |7 U; M; ohave established a large number of hiPSCs derived from9 L( O9 a% f" Z1 m
various human tissues and have obtained their DNA0 d- a' S% G) o' M
methylation profiles. Comparison analyses indicated that0 D9 |' M- \, X% S0 D) q% h. u
the epigenetic patterns of various hiPSCs, irrespective of! J) X4 ]2 W  ^7 J4 c+ `$ z, Z
their source tissue, were very similar to one another and
( `! P/ k; O+ a: U1 ?were similar to those of human embryonic stem cells7 z: y' S2 \4 E' O, X
(hESCs). However, the profiles of hiPSCs and hESCs# m6 q) S9 n1 R& Y
exhibited epigenetic differences, which were caused by
- j! c! @! F/ v, Nrandom aberrant hypermethylation at early passages.; j& Z! Z5 {  W
Interestingly, continuous passaging of the hiPSCs diminished
% v+ a# n9 s8 Bthe differences between DNA methylation profiles of& C5 `% |, u9 }& v1 c, U
hiPSCs and hESCs. The number of aberrant DNA methylation6 b: y0 I0 r- y& R/ k  |9 U1 b- Y, d
regions may thus represent a useful epigenetic index