scholarly journals Histone Deacetylase 1 Deficiency Impairs Differentiation and Electrophysiological Properties of Cardiomyocytes Derived from Induced Pluripotent Cells

Stem Cells ◽  
2012 ◽  
Vol 30 (11) ◽  
pp. 2412-2422 ◽  
Author(s):  
Eneda Hoxha ◽  
Erin Lambers ◽  
Hehuang Xie ◽  
Alexandre De Andrade ◽  
Prasanna Krishnamurthy ◽  
...  
PLoS Biology ◽  
2009 ◽  
Vol 7 (2) ◽  
pp. e1000042 ◽  
Author(s):  
Katriina Aalto-Setälä ◽  
Bruce R Conklin ◽  
Bernard Lo

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 269 ◽  
Author(s):  
Long H. Do ◽  
William C. Mobley ◽  
Nishant Singhal

Recently, in studies examining fibroblasts obtained from the tissues of one set of monozygotic twins (i.e. fetuses derived from the same egg) discordant for trisomy 21 (Down syndrome; DS), Letourneau et al., reported the presence of a defined pattern of dysregulation within specific genomic domains they referred to as Gene Expression Dysregulated Domains (GEDDs). GEDDs were described as alternating segments of increased or decreased gene expression affecting all chromosomes. Strikingly, GEDDs in fibroblasts were largely conserved in induced pluripotent cells (iPSCs) generated from the twin’s fibroblasts as well as in fibroblasts from the Ts65Dn mouse model of DS. Our recent analysis failed to find GEDDs. We reexamined the human iPSCs RNAseq data from Letourneau et al., and data from this same research group published earlier examining iPSCs from the same monozygotic twins. An independent analysis of RNAseq data from Ts65Dn fibroblasts also failed to confirm presence of GEDDs. Our analysis questions the validity of GEDDs in DS.


2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Eneda Hoxha ◽  
Erin Lambers ◽  
Veronica Ramirez ◽  
Prasanna Krishnamurthy ◽  
Suresh Verma ◽  
...  

Cardiomyocytes derived from embryonic and induced pluripotent stem cells (ES/iPS) provide an excellent source for cell replacement therapies following myocardial ischemia. However, some of the obstacles in the realization of the full potential of iPS/ES cells arise from incomplete and poorly understood molecular mechanisms and epigenetic modifications that govern their cardiovascular specific differentiation. We identified Histone Deacetylase 1 (HDAC1) as a crucial regulator in early differentiation of mES and iPS cells. We propose a novel pathway in which HDAC1 regulates cardiovascular differentiation by regulating SOX17 which in turn regulates BMP2 signaling in differentiating pluripotent cells. Utilizing stable HDAC1 knock-down (HDAC1-KD) cell lines, we report an essential role for HDAC1 in deacetylating regulatory regions of pluripotency-associated genes during early cardiovascular differentiation. HDAC1-KD cells show severely repressed cardiomyocyte differentiation potential. We propose a novel HDAC1-BMP2-SOX17 dependent pathway through which deacetylation of pluripotency associated genes leads to their suppression and allows for early cardiovascular-associated genes to be expressed and differentiation to occur. Furthermore, we show that HDAC1 affects DNA methylation both during pluripotency and differentiation and plays a crucial, non-redundant role in cardiovascular specific differentiation and cardiomyocyte maturation. Our data elucidates important differences between ES and iPS HDAC1-KD cells that affect their ability to differentiate into cardiovascular lineages. 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 therapeutic applications in regenerative medicine. Further research in the molecular mechanisms involved in this process will greatly aid our understanding of the epigenetic circuitry of pluripotency and differentiation in pluripotent cells.


Haematologica ◽  
2018 ◽  
Vol 103 (5) ◽  
pp. e188-e191 ◽  
Author(s):  
Shunsuke Hatta ◽  
Tohru Fujiwara ◽  
Takako Yamamoto ◽  
Kei Saito ◽  
Mayumi Kamata ◽  
...  

2015 ◽  
Vol 24 (3) ◽  
pp. 393-402 ◽  
Author(s):  
Young Tae Heo ◽  
Xiaoyuan Quan ◽  
Yong Nan Xu ◽  
Soonbong Baek ◽  
Hwan Choi ◽  
...  

Stem Cells ◽  
2011 ◽  
Vol 29 (8) ◽  
pp. 1196-1205 ◽  
Author(s):  
Yuki Hasegawa ◽  
Naoko Takahashi ◽  
Alistair R. R. Forrest ◽  
Jay W. Shin ◽  
Yohei Kinoshita ◽  
...  

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