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& k' o* A  K+ I- E1 E! ?" t' b2 b( Y
(hiPSCs) are considered to be powerful tools in regenerative
9 H( G9 F" K4 N8 w4 l4 Smedicine. To enable the use of hiPSCs in the field of* i9 Y  T/ U* B8 V0 G. E
regenerative medicine, it is necessary to understand the8 u' @! z( {) m
mechanisms of reprogramming during the transformation$ G% r  r/ y! n8 [
of somatic cells into hiPSCs. Genome-wide epigenetic- ~6 |& g; c1 u7 z4 U
modification constitutes a critical event in the generation of
* h8 z" t0 A) L5 L" s+ z, f/ siPSCs. In other words, to analyze epigenetic changes in2 ~2 y5 j- ~' r' e1 c3 c
iPSCs means to elucidate reprogramming processes. We  a& X. v0 W/ y' X& a* {: {- e7 R$ _
have established a large number of hiPSCs derived from; O6 i$ s! B. x
various human tissues and have obtained their DNA
+ |+ ~, T, {1 fmethylation profiles. Comparison analyses indicated that
) G; M6 T$ ~/ L- Q1 }, p) r+ mthe epigenetic patterns of various hiPSCs, irrespective of( x( s4 S7 I6 O( P
their source tissue, were very similar to one another and
. x* T& a1 q% y3 ?" F7 V4 }( f' hwere similar to those of human embryonic stem cells6 t! a1 D# m2 r: f( f- }& ~8 z( G
(hESCs). However, the profiles of hiPSCs and hESCs
! N) _4 Y: j5 l7 sexhibited epigenetic differences, which were caused by
  k1 r1 t: n: ]( P, xrandom aberrant hypermethylation at early passages.3 S. V' Q8 j0 `. L# Q
Interestingly, continuous passaging of the hiPSCs diminished
5 W/ G3 u' {' K% Q. h  @' Q7 uthe differences between DNA methylation profiles of; J2 p" B& K* Z6 Y; u
hiPSCs and hESCs. The number of aberrant DNA methylation
  H9 i( ?# K3 Kregions may thus represent a useful epigenetic index