DNA methylation dynamics in human induced pluripotent stem cells

Tlexander

DNA methylation dynamics in human induced pluripotent stem cells+ S. V2 H# @6 \

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Abstract Indeed human induced pluripotent stem cells4 m0 g  a" S2 @3 k  R1 O' e
(hiPSCs) are considered to be powerful tools in regenerative
0 _- M% r! A; Nmedicine. To enable the use of hiPSCs in the field of4 \, B! e8 X* a9 B8 N
regenerative medicine, it is necessary to understand the  G( I6 ?' l3 b6 ?0 e" g% y
mechanisms of reprogramming during the transformation
/ S) w+ e, H! o8 ]6 R% C5 dof somatic cells into hiPSCs. Genome-wide epigenetic) F7 b5 t1 h. u& w7 }
modification constitutes a critical event in the generation of- v2 d2 G( X8 H  Q& f' B+ N
iPSCs. In other words, to analyze epigenetic changes in
/ v3 D3 t6 i& G, j3 CiPSCs means to elucidate reprogramming processes. We
5 j# @1 U9 n3 H' [have established a large number of hiPSCs derived from% Y3 Z. |! @! E: f+ K& J
various human tissues and have obtained their DNA
. z( h- T& g7 `methylation profiles. Comparison analyses indicated that
" ]1 q; c- I7 E# c. Cthe epigenetic patterns of various hiPSCs, irrespective of
, C$ W  o7 @* k, Z8 A" c" wtheir source tissue, were very similar to one another and
% _3 q% h- t/ X( C4 w7 nwere similar to those of human embryonic stem cells; n$ E; @& V$ ~2 G+ [8 I$ n' G8 h
(hESCs). However, the profiles of hiPSCs and hESCs
( R) a* \+ m% b% Y& t+ Texhibited epigenetic differences, which were caused by
4 D( q4 ~! W, f5 Irandom aberrant hypermethylation at early passages.
7 \4 h3 [& w2 _; j" e  |( uInterestingly, continuous passaging of the hiPSCs diminished
3 }- o+ v* T- |5 h- O2 e8 Mthe differences between DNA methylation profiles of+ D, x" @$ B5 _! A  D0 d
hiPSCs and hESCs. The number of aberrant DNA methylation! k1 Q5 J( x4 D3 I
regions may thus represent a useful epigenetic index