The use of signalling pathway inhibitors and chromatin modifiers for enhancing pluripotency

Sümer, Hüseyin; Liu, Jun; Verma, Paul J.

doi:10.1016/j.theriogenology.2010.05.030

Cited by 7 publications

(4 citation statements)

References 90 publications

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“…The prevailing view is that incomplete epigenetic reprogramming of donor cell nuclei and resulting aberrant gene expression during development [2], [5]–[7]. To facilitate nuclear reprogramming and thus improve cloning efficiency, several methods, including treating the donor cells and/or early nuclear transferred embryos with DNMT1 inhibitors (DNMTi) like 5-aza-20-deoxycytidine (5-aza-dC) and histone deacetylatse inhibitors (HDACi) like TSA and scriptaid, have been tested to assist the somatic nucleus to mimic DNA methylation and chromatin remodeling[6], [8]–[9].…”

Section: Introductionmentioning

confidence: 99%

Effects of DNMT1 and HDAC Inhibitors on Gene-Specific Methylation Reprogramming during Porcine Somatic Cell Nuclear Transfer

et al. 2013

PLoS ONE

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Somatic cell nuclear transfer (SCNT) in mammalian cloning currently remains inefficient. Incomplete or erroneous epigenetic reprogramming of specialized donor somatic nuclear and resulting aberrant gene expression during development of cloned embryos is commonly believed as the main reason that causes the low efficiency of SCNT. Use of small molecular reprogramming modifiers to assist the somatic nucleus to mimic naturally occurring DNA methylation and chromatin remodeling in nucleus of fertilization-derived zygotes, has been widely attempted to improve cloning efficiency. However, impacts of these small modifiers on gene-specific methylation dynamics and their potential effects on methylation of imprinted gene have rarely been traced. Here, we attempted two relatively novel DNMT1 inhibitor (DNMTi) and histone deacetylase inhibitor (HDACi), scriptaid and RG108, and demonstrated their effects on dynamics of gene-specific DNA methylation and transcription of porcine SCNT embryos. We found that scriptaid and RG108 had synergetic effects on rescuing the disrupted methylation imprint of H19 during SCNT at least partially by repression over-expressed MBD3 in eight-cell cloned embryos. Furthermore, we firstly identified a differential methylation regions (DMRs) at 5′ flanking regions of XIST gene and found that scriptaid alone and its combination with RG108 modify the dynamics of both transcription and DNA methylation levels in cloned embryos, by different manners. Additionally, we found that scriptaid alone and its combination with RG108 can significantly promote the transcription of NANOG in cloned embryos and enhance their pre-implantation developmental capacity. Our results would contribute to uncovering the epigenetic reprogramming mechanisms underlying the effects of assisted small molecules on improvement of mammalian cloning efficiency.

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Section: Introductionmentioning

confidence: 99%

Effects of DNMT1 and HDAC Inhibitors on Gene-Specific Methylation Reprogramming during Porcine Somatic Cell Nuclear Transfer

et al. 2013

PLoS ONE

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“…The regulatory mechanisms and signal transductions of self-renewal, differentiation, proliferation, and apoptosis [41,42,124], as well as the corresponding inhibitors of stem cells [43][44][45][46][47]125] have been investigated (Figure 1). …”

Section: Pluripotent Signaling Pathwaysmentioning

confidence: 99%

Conditions and Techniques for Mouse Embryonic Stem Cell Derivation and Culture

Lee¹

2013

Pluripotent Stem Cells

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“…Similarly, the H3 histones may also be demethylated when genes become active, opening the chromatin and making the DNA more accessible to transcriptional machinery. The addition of agents that alter chromatin structure and DNA methylation states have been used as media supplements to enhance the reprogramming of iPS cells [34]. …”

Section: Characterization Of Es/ips Cells and Evaluation Of Pluripotencymentioning

confidence: 99%

Embryonic Stem Cells and iPS Cells: Sources and Characteristics

Hackett

Fortier

2011

Veterinary Clinics of North America: Equine Practice

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Synopsis The field of regenerative medicine research is rapidly expanding for both human and animal model organisms. One area of particular interest to many equine researchers is the possibility of isolating or generating cells that are pluripotent, therefore capable of producing differentiated cell types derived from all three primary germ layers. Currently, several reports of equine embryonic stem-like (ES) cell isolation can be found in the literature. Meanwhile, other groups are working to produce equine induced pluripotent stem (iPS) cells. The focus of this chapter is to provide a background summary of the essential features needed to characterize a cell type as pluripotent in any species, specific challenges in using the horse as a model organism for pluripotent cell generation, and a brief introduction of current and upcoming clinical trials using ES/iPS cells.

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The use of signalling pathway inhibitors and chromatin modifiers for enhancing pluripotency

Cited by 7 publications

References 90 publications

Effects of DNMT1 and HDAC Inhibitors on Gene-Specific Methylation Reprogramming during Porcine Somatic Cell Nuclear Transfer

Effects of DNMT1 and HDAC Inhibitors on Gene-Specific Methylation Reprogramming during Porcine Somatic Cell Nuclear Transfer

Conditions and Techniques for Mouse Embryonic Stem Cell Derivation and Culture

Embryonic Stem Cells and iPS Cells: Sources and Characteristics

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