DNA methylation dynamics in human induced pluripotent stem cells

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DNA methylation dynamics in human induced pluripotent stem cells( O7 i  B" g# w6 M* W9 \- s
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; k5 S; t" \; B0 F3 f% AAbstract Indeed human induced pluripotent stem cells
' u) E7 d8 Z7 p, s(hiPSCs) are considered to be powerful tools in regenerative
, l6 V# O8 [& S. n) e; w" nmedicine. To enable the use of hiPSCs in the field of2 y. G& o- i2 v1 P8 i
regenerative medicine, it is necessary to understand the0 ]0 m6 ]8 o1 i- f! F
mechanisms of reprogramming during the transformation
* d+ T& _8 b5 h+ {* Uof somatic cells into hiPSCs. Genome-wide epigenetic
/ O( H& G/ b& t% p  e% l  L# lmodification constitutes a critical event in the generation of# F7 }& ^8 u0 W) v* v2 Y
iPSCs. In other words, to analyze epigenetic changes in
$ J3 D+ q- r( ?  E: ?8 IiPSCs means to elucidate reprogramming processes. We
( B) D; I6 u/ T. _! I6 Khave established a large number of hiPSCs derived from
4 q# A5 ~8 i4 _; |7 a. Jvarious human tissues and have obtained their DNA$ R1 D( ]8 K  k7 s$ D8 q: J" e) T
methylation profiles. Comparison analyses indicated that0 Q' L9 A; `% e- {' [
the epigenetic patterns of various hiPSCs, irrespective of
0 }# h% d; `/ i+ Mtheir source tissue, were very similar to one another and1 F1 c7 B) X/ e  Q% J. F" o! @
were similar to those of human embryonic stem cells
: G' l  I& r- Q3 q5 }% C( i(hESCs). However, the profiles of hiPSCs and hESCs
( S4 Q& B6 h4 D: A3 nexhibited epigenetic differences, which were caused by
6 K+ g( }  r* e# m) J' O; B: h  krandom aberrant hypermethylation at early passages.
2 l1 r- d' l% i! a7 `Interestingly, continuous passaging of the hiPSCs diminished
9 H$ \, G4 l; I' f5 l# q/ I& Q# Nthe differences between DNA methylation profiles of! i/ [7 l. E4 g$ L. }" M- D
hiPSCs and hESCs. The number of aberrant DNA methylation
7 d# \  S7 M7 K3 H$ N6 t: g5 ~regions may thus represent a useful epigenetic index