DNA methylation dynamics in human induced pluripotent stem cells

Tlexander

DNA methylation dynamics in human induced pluripotent stem cells2 C7 R( e5 X* C, u- P2 f

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6 U: ]; r) W9 C. X1 iAbstract Indeed human induced pluripotent stem cells$ y5 O+ \$ ]3 H
(hiPSCs) are considered to be powerful tools in regenerative
- `& Y  G/ b4 k- b* {. u' `7 n+ |0 Amedicine. To enable the use of hiPSCs in the field of4 r) D/ ~/ v6 ~* ]' T6 U
regenerative medicine, it is necessary to understand the
4 r; d: p$ @" l! b" E% p6 Q. Lmechanisms of reprogramming during the transformation
) d8 \$ ~9 z+ g; R9 ^# E' M5 h2 q3 Dof somatic cells into hiPSCs. Genome-wide epigenetic# t: z" h+ G8 r) g
modification constitutes a critical event in the generation of
! K$ O2 H, B% RiPSCs. In other words, to analyze epigenetic changes in
9 S1 E. Y. u* F2 f; y5 xiPSCs means to elucidate reprogramming processes. We
: Q8 _& u. q) C3 [9 Y0 @have established a large number of hiPSCs derived from6 M: F6 Z8 y- E. i5 |- P5 D, p
various human tissues and have obtained their DNA/ @. d4 Q  Y. b
methylation profiles. Comparison analyses indicated that( ^! l  z% }' n" l. M* _; D$ Z" p6 a
the epigenetic patterns of various hiPSCs, irrespective of7 W: x5 _# H' Y3 I; ?+ g) H5 Z) O
their source tissue, were very similar to one another and
- ]  G3 n2 s2 E5 q; Rwere similar to those of human embryonic stem cells* g/ U0 b& @' {" a. _- s
(hESCs). However, the profiles of hiPSCs and hESCs
1 ?# J$ r) M9 aexhibited epigenetic differences, which were caused by0 o9 j1 O$ K- Z8 L; k  H- x# S7 y
random aberrant hypermethylation at early passages.
$ D, d/ r: t- W5 L+ BInterestingly, continuous passaging of the hiPSCs diminished* ]: v6 y$ |8 x8 O( C9 E* o
the differences between DNA methylation profiles of$ \4 E1 }5 Z- J. J5 s1 f4 r5 x4 x
hiPSCs and hESCs. The number of aberrant DNA methylation
" C9 h: N$ b7 M1 b' Vregions may thus represent a useful epigenetic index