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DNA methylation and cellular reprogramming.pdf
' a( v, {; }$ D, m% O6 h( B$ A3 K- l- s$ z1 L( O8 l! N
4 p1 ]+ \3 W, LThe recent discovery that a small number of defined' ^7 P, A* J% ^' w
factors are sufficient to reprogram somatic cells into
! j& {3 D& F, F. {pluripotent stem cells has significantly expanded our& W6 o& { H7 }* S( D9 V+ c: }
knowledge of the plasticity of the epigenome. In this) v4 v. o2 \4 t7 T/ O; \ E
review we discuss some aspects of cell fate plasticity and5 q, w) g# s$ P# M3 A8 p$ v6 T4 g0 ]
epigenetic alterations, with emphasis on DNA methylation
9 l* u$ Y1 x4 v! L3 aduring cellular reprogramming. Recent data suggest
7 Q9 p Y& n! S* Qthat DNA methylation is a major barrier to induced- w3 @9 V+ H* O
pluripotent stem (iPS) cell reprogramming. The! E8 I V% ?: N" J& r9 p
demethylating agent 5-azacytidine can enhance the efficiency# l B' n0 b+ C1 t
of iPS cells generation and the putative DNA
% r+ E; t/ C$ w# M( {demethylase protein activation-induced cytidine deaminase5 j7 R, ~( ~( M7 \& T: [4 N
(AID/AICDA) can erase DNA methylation at pluripotency1 I; e7 K, R# _3 w. E8 h5 q
gene promoters, thereby allowing cellular! u t: ^# n; ^; y% [7 a( B" ~
reprogramming. Elucidation of the epigenetic changes
- w$ ?+ ~; _1 z% o/ B1 ?, x/ Qtaking place during cellular reprogramming will enhance; N8 ]& A$ u* M
our understanding of stem cell biology and facilitate4 H, h) O! \9 r1 R9 _! a6 F
therapeutic applications. |
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