DNA methylation dynamics in human induced pluripotent stem cells

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DNA methylation dynamics in human induced pluripotent stem cells4 V& u. Q0 ?4 \7 ]

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' H$ _, T" u9 _' U0 b# E+ lAbstract Indeed human induced pluripotent stem cells
; r0 W3 j2 u: \  o3 i$ ^' e(hiPSCs) are considered to be powerful tools in regenerative1 ]+ t7 M6 d- a! k  r. ]/ n8 S
medicine. To enable the use of hiPSCs in the field of
$ p4 J/ M, \3 L6 ^regenerative medicine, it is necessary to understand the
0 ]5 C& h0 g# Z* t% y" Wmechanisms of reprogramming during the transformation
8 {1 Z- T! c0 ~! C0 oof somatic cells into hiPSCs. Genome-wide epigenetic
" U# [4 d+ H* C7 C( }+ h8 ^modification constitutes a critical event in the generation of$ y- D2 u$ p& |9 G% J; [  H
iPSCs. In other words, to analyze epigenetic changes in
2 N4 V- r% j6 x) K* KiPSCs means to elucidate reprogramming processes. We
; e9 i& {" W1 S( N: m$ qhave established a large number of hiPSCs derived from
" K6 T+ F, a* ?) x1 a& Xvarious human tissues and have obtained their DNA
3 o( y( X6 V1 x4 Smethylation profiles. Comparison analyses indicated that- }: Y( J( C2 x6 R
the epigenetic patterns of various hiPSCs, irrespective of9 N  w) s7 U5 c- ~
their source tissue, were very similar to one another and
; k' ~& a2 D2 s3 awere similar to those of human embryonic stem cells4 J# }3 r2 ]2 t  v, d7 {  X
(hESCs). However, the profiles of hiPSCs and hESCs) g( r, l' Y, [4 o/ }3 ^
exhibited epigenetic differences, which were caused by1 W2 E, a; s/ Z6 B5 e2 y
random aberrant hypermethylation at early passages.
/ T  b! b7 x) @+ a. nInterestingly, continuous passaging of the hiPSCs diminished8 o! b+ E* D6 T+ ]7 \5 ]) U
the differences between DNA methylation profiles of
. F4 I# d. |* c  ShiPSCs and hESCs. The number of aberrant DNA methylation( O5 Z0 p% ]5 |! U  }" o
regions may thus represent a useful epigenetic index