Histone deacetylase 1 deficiency impairs differentiation and electrophysiological properties of cardiomyocytes derived from induced pluripotent cells.
Histone deacetylase 1 deficiency impairs differentiation and electrophysiological properties of cardiomyocytes derived from induced pluripotent cells.
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DOI：
10.1002/stem.1209
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发表时间：
2012-11
期刊：
影响因子：
5.2
通讯作者：
Kishore, Raj
中科院分区：
文献类型：
--
作者：
Hoxha, Eneda;Lambers, Erin;Xie, Hehuang;De Andrade, Alexandre;Krishnamurthy, Prasanna;Wasserstrom, John A.;Ramirez, Veronica;Thal, Melissa;Verma, Suresh K.;Soares, Marcelo B.;Kishore, Raj
关键词：
表观遗传和染色质修饰在胚胎和诱导多能干细胞（ES和iPS细胞）中起着特别重要的作用，允许细胞分化和去分化回到多能状态。我们分析了一种关键的染色质修饰酶，组蛋白脱乙酰酶1（HDAC 1）的丢失如何影响ES和iPS细胞的早期和心血管分化。我们还研究了诱导分化时这两种细胞类型之间的潜在差异。我们的数据表明HDAC1在早期分化过程中对关键多能性相关基因的调节区域进行脱乙酰化中起着重要作用。虽然HDAC1主要作为组蛋白脱乙酰酶发挥作用，但其缺失也会影响ES和iPS细胞在多能性和分化过程中的DNA甲基化。我们发现HDAC1在心肌细胞分化和成熟中起着至关重要的、非冗余的作用。我们的数据还阐明了ES和iPS细胞之间的重要差异，当这种酶的水平降低时，会影响它们分化为功能性心肌细胞的能力。由于不同水平的染色质修饰酶可能存在于患者来源的iPS细胞中，因此了解ES和iPS细胞中这些酶的分子电路对于它们在心血管治疗应用中的潜在用途至关重要。
Epigenetic and chromatin modifications play particularly important roles in Embryonic and induced Pluripotent Stem cells (ES and iPS cells) allowing for the cells to both differentiate and dedifferentiate back to a pluripotent state. We analyzed how the loss of a key chromatin modifying enzyme, histone deacetylase 1(HDAC1), affects early and cardiovascular differentiation of both ES and iPS cells. We also investigated potential differences between these two cell types when differentiation is induced. Our data indicates an essential role for HDAC1 in deacetylating regulatory regions of key pluripotency-associated genes during early differentiation. Although HDAC1 functions primarily as a histone deacetylase, its loss also affects DNA methylation in ES and iPS cells both during pluripotency and differentiation. We show that HDAC1 plays a crucial, non-redundant role in cardiomyocyte differentiation and maturation. Our data also elucidates important differences between ES and iPS cells, when levels of this enzyme are reduced, that affect their ability to differentiate into functional cardiomyocytes. As varying levels of chromatin modifying enzymes are likely to exist in patient derived iPS cells, understanding the molecular circuitry of these enzymes in ES and iPS cells is critical for their potential use in cardiovascular therapeutic applications.
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影响因子：
14.9
作者：
Xie H;Wang M;Bonaldo Mde F;Smith C;Rajaram V;Goldman S;Tomita T;Soares MB
通讯作者：
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