alexa The Dynamics of Global Chromatin Remodeling are Pivotal for Tracking the Normal Pluripotency of Human Embryonic Stem Cells | OMICS International | Abstract
ISSN: 2161-0940

Anatomy & Physiology: Current Research
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Research Article

The Dynamics of Global Chromatin Remodeling are Pivotal for Tracking the Normal Pluripotency of Human Embryonic Stem Cells

Xuejun H. Parsons1,2*

1 San Diego Regenerative Medicine Institute, San Diego, CA 92109, USA

2 Xcelthera, San Diego, CA 92109, USA

*Corresponding Author:
Xuejun H. Parsons
San Diego Regenerative Medicine Institute and Xcelthera
San Diego, CA 92109, USA
Tel: +858-274-1621
Fax: +858-581-3213
E-mail: [email protected]

Received date February 28, 2011; Accepted date March 27, 2012; Published date April 26, 2012

Citation: Parsons XH (2012) The Dynamics of Global Chromatin Remodeling are Pivotal for Tracking the Normal Pluripotency of Human Embryonic Stem Cells. Anat Physiol S3:002. doi: 10.4172/2161-0940.S3-002

Copyright: © 2012 Parsons XH. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Pluripotent Human Embryonic Stem Cells (hESCs) have the unconstrained capacity for long-term stable undifferentiated growth in culture and unrestricted developmental capacity. Packaging of the eukaryotic genome into chromatin confers higher order structural control over maintaining stem cell plasticity and directing differentiation. We recently reported the establishment of a defined culture system for sustaining the epiblast pluripotence of hESCs, serving as a platform for de novo derivation of clinically-suitable hESCs and effectively directing such hESCs uniformly towards functional lineages. To unveil the epigenetic mechanism in maintaining the epiblast pluripotence of hESCs, in this study, the global chromatin dynamics in the pluripotent hESCs maintained under the defined culture were examined. This study shows that the genomic plasticityof pluripotent hESCs is enabled by an acetylated globally active chromatin maintained by Oct-4. The pluripotency of hESCs that display normal stable expansion is associated with high levels of expression and nuclear localization of active chromatin remodeling factors that include acetylated histone H3 and H4, Brg-1, hSNF2H, HAT p300, and HDAC1; weak expression or cytoplasmic localization of repressive chromatin remodeling factors that are implicated in transcriptional silencing; and residual H3 K9 methylation. A dynamic progression from acetylated to transient hyperacetylated to hypoacetylated chromatin states correlates with loss-of-Oct4-associated hESC differentiation. RNA interference directed against Oct-4 and HDAC inhibitor analysis support this pivotal link between chromatin dynamics and hESC differentiation. These findings reveal an epigenetic mechanism for placing global chromatin dynamics as central to tracking the normal pluripotency and lineage progression of hESCs.

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