DNA methylation dynamics in human induced pluripotent stem cells

Tlexander

DNA methylation dynamics in human induced pluripotent stem cells1 [* Q4 L+ Y# x& n2 m3 S

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Abstract Indeed human induced pluripotent stem cells+ q, ^- E: K! p. _
(hiPSCs) are considered to be powerful tools in regenerative& T2 G$ t1 p5 ^2 V- L* F
medicine. To enable the use of hiPSCs in the field of
* [; g/ \/ i! g3 X0 rregenerative medicine, it is necessary to understand the. |9 a7 [0 Z6 l2 T
mechanisms of reprogramming during the transformation
  X$ b& Z% s/ ]& ]5 o1 ]: Lof somatic cells into hiPSCs. Genome-wide epigenetic! n3 V+ H5 k( t5 b5 n
modification constitutes a critical event in the generation of
: n" V7 q' M8 @' j9 B0 z* z/ JiPSCs. In other words, to analyze epigenetic changes in
. }$ r( F+ f6 X8 a: _4 `iPSCs means to elucidate reprogramming processes. We7 C' f* L% M) E/ y2 ^
have established a large number of hiPSCs derived from5 h! q: J7 [& F: \6 w) |  t
various human tissues and have obtained their DNA  k' w9 F& E" m2 W: ~" d
methylation profiles. Comparison analyses indicated that: i; Z: p* E+ n5 y, D( x, P
the epigenetic patterns of various hiPSCs, irrespective of
  F% _4 ~2 h* n6 Z+ Q9 stheir source tissue, were very similar to one another and8 L' ], Y& z) O3 H6 O9 g: A0 a% H+ H
were similar to those of human embryonic stem cells
/ x! `' A; K$ {(hESCs). However, the profiles of hiPSCs and hESCs
) r+ I; O: F4 n* Z/ i8 Zexhibited epigenetic differences, which were caused by* c! K9 R( {$ Z+ p" E
random aberrant hypermethylation at early passages.) g. }' [# L& c/ h5 t- T$ J7 s
Interestingly, continuous passaging of the hiPSCs diminished8 P& A4 B( Z0 J
the differences between DNA methylation profiles of" G1 c! J- v! [# [3 T% A
hiPSCs and hESCs. The number of aberrant DNA methylation; }3 J& R9 n9 ~* H2 C6 Q
regions may thus represent a useful epigenetic index