DNA methylation dynamics in human induced pluripotent stem cells

Tlexander

DNA methylation dynamics in human induced pluripotent stem cells
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Abstract Indeed human induced pluripotent stem cells
: d6 a' d1 ^2 \+ Z8 t! S(hiPSCs) are considered to be powerful tools in regenerative( v- L& h% q+ j* C& G
medicine. To enable the use of hiPSCs in the field of, _6 I! l4 k- N9 X4 M
regenerative medicine, it is necessary to understand the. Y3 e1 x, Q/ S& C& l. P
mechanisms of reprogramming during the transformation
+ ~6 m& E5 V3 o5 `& xof somatic cells into hiPSCs. Genome-wide epigenetic* G9 K  B6 `) i
modification constitutes a critical event in the generation of
8 b4 ~6 j- `% qiPSCs. In other words, to analyze epigenetic changes in
, x, M3 w/ o; y8 ~) k% ~4 {( kiPSCs means to elucidate reprogramming processes. We1 P. l( J) n' A
have established a large number of hiPSCs derived from5 `4 y# y# X; f* I
various human tissues and have obtained their DNA
1 i6 V# r2 v3 i% Mmethylation profiles. Comparison analyses indicated that
& a6 |  |" _% z# n! vthe epigenetic patterns of various hiPSCs, irrespective of, u  G8 W5 W6 o
their source tissue, were very similar to one another and
% }& R! q5 }: [* `9 ^0 ?0 P* ]were similar to those of human embryonic stem cells
& n6 [& m7 C/ d; M/ W( }(hESCs). However, the profiles of hiPSCs and hESCs; ]( f7 L8 W: ^8 o
exhibited epigenetic differences, which were caused by
& q2 G7 A1 T& f! Y/ Q7 c1 v& qrandom aberrant hypermethylation at early passages.
7 b5 J3 @# q: l6 `# O4 c8 o1 r( FInterestingly, continuous passaging of the hiPSCs diminished/ V5 G# r  Y/ L- Q  h
the differences between DNA methylation profiles of
3 _1 B' |2 }3 |4 k: C7 ZhiPSCs and hESCs. The number of aberrant DNA methylation& v0 Q7 m1 L( u) D' h
regions may thus represent a useful epigenetic index