Directed transdifferentiation of mouse mesoderm to3 p. B# h* c, Z7 [
heart tissue by defined factors $ V" p; o' R: c6 e! p: q% S/ b8 VJun K. Takeuchi1,2 & Benoit G. Bruneau1,3! U$ i/ D: W: J' y" o @4 r7 m* w
Heart disease is the leading cause of mortality and morbidity in the% s V1 O9 E9 V+ L% }5 r0 n
western world. The heart has little regenerative capacity after & M' c. v' {: B) Tdamage, leading to much interest in understanding the factors 0 P+ B3 o" a. g. U0 W6 e4 I* `required to produce new cardiac myocytes. Despite a robust 9 J! m* p+ U' Hunderstanding of the molecular networks regulating cardiac/ m! O% l( ]1 f9 F% k+ e
differentiation1,2, no single transcription factor or combination . ^' `% n3 q3 p V- b: x+ k3 r) `8 Tof factors has been shown to activate the cardiac gene program( s+ k d: l2 h2 o' m0 b8 _6 A1 f
de novo in mammalian cells or tissues. Here we define the minimal% G, A& a" \8 C* v# a7 x2 r
requirements for transdifferentiation of mouse mesoderm to - s( Q! c: d* y3 G/ A5 I3 ~cardiac myocytes. We show that two cardiac transcription factors, 2 c2 t4 C* {, ?: _( f/ }/ ? }# zGata4 and Tbx5, and a cardiac-specific subunit of BAF chromatinremodelling * D5 f& G K$ ~. Wcomplexes, Baf60c (also called Smarcd3), can direct 0 X( W, P C% S3 m! F, o4 hectopic differentiation of mouse mesoderm into beating cardiomyocytes,. k5 F7 t3 g6 v8 _0 c7 w* d) t
including the normally non-cardiogenic posterior* P5 ~! F8 h' E2 Z& s7 D' |8 l! A* A
mesoderm and the extraembryonic mesoderm of the amnion. - \3 @9 v- e, f& W K7 gGata4 with Baf60c initiated ectopic cardiac gene expression.6 s/ c& m9 [& b$ H' z0 g. ^) Y3 q& u. O
Addition of Tbx5 allowed differentiation into contracting cardiomyocytes 0 j3 m/ D) p$ N2 W8 Q8 I$ _7 a1 Pand repression of non-cardiac mesodermal genes. 4 J! d6 O& h+ q, F1 wBaf60c was essential for the ectopic cardiogenic activity of Gata40 d. w& ?/ ?+ D5 S
and Tbx5, partly by permitting binding of Gata4 to cardiac genes,! ^; O& O' p/ ] W. [
indicating a novel instructive role for BAF complexes in tissuespecific4 q- ^( O; r* |9 Y
regulation. The combined function of these factors establishes k$ ]# z: u$ C# O! z: |* H* N
a robust mechanism for controlling cellular differentiation,5 ]( i; c% h, p% A. e5 `5 \. K
and may allow reprogramming of new cardiomyocytes for regenerative9 H1 a( Y8 _ T- W( b$ C* |
purpose作者: jianlindunev 时间: 2010-5-6 23:41
[attach]7399[/attach]小鼠中胚层至心脏组织的直接转分化过程的影响因素已经确定2 a, I' B; I) Y
（4因子-Gata4 and Tbx5，NKX2.5,Baf60c）作者: wangyan9672 时间: 2010-5-20 08:54