Germline Recruitment in Mice: A Genetic Program for Epigenetic Reprogramming

2006 ◽  
pp. 143-174 ◽  
Author(s):  
Y. Ohinata ◽  
Y. Seki ◽  
B. Payer ◽  
D. O’Carroll ◽  
M. A. Surani ◽  
...  
Keyword(s):  
Genetic Program ◽  
Epigenetic Reprogramming

scholarly journals Mechanism of Mouse Germ Cell Specification: A Genetic Program Regulating Epigenetic Reprogramming

2004 ◽  
Vol 69 (0) ◽  
pp. 1-10 ◽  
Author(s):  
M.A. SURANI ◽  
K. ANCELIN ◽  
P. HAJKOVA ◽  
U.C. LANGE ◽  
B. PAYER ◽  
...  
Keyword(s):  
Germ Cell ◽  
Genetic Program ◽  
Epigenetic Reprogramming ◽  
Cell Specification ◽  
Germ Cell Specification

NREP Bridges TGF-ß Signaling and Lipid Metabolism in the Epigenetic Reprogramming of NAFLD in the Offspring of Insulin-Resistant Parents

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 46-OR
Author(s):  
DARIO F. DE JESUS ◽  
KAZUKI ORIME ◽  
CHIH-HAO WANG ◽  
JIANG HU ◽  
ERCUMENT DIRICE ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Epigenetic Reprogramming ◽  
Insulin Resistant

scholarly journals The Selective Histone Deacetylase Inhibitor MI192 Enhances the Osteogenic Differentiation Efficacy of Human Dental Pulp Stromal Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5224
Author(s):  
Kenny Man ◽  
Liam Lawlor ◽  
Lin-Hua Jiang ◽  
Xuebin B. Yang
Keyword(s):  
Alkaline Phosphatase ◽  
Osteogenic Differentiation ◽  
Stromal Cells ◽  
Dental Pulp ◽  
Selective Inhibitor ◽  
Epigenetic Reprogramming ◽  
Type I ◽  
Human Dental Pulp ◽  
Pre Treatment ◽  
Dose Dependent

The use of human dental pulp stromal cells (hDPSCs) has gained increasing attention as an alternative stem cell source for bone tissue engineering. The modification of the cells’ epigenetics has been found to play an important role in regulating differentiation, with the inhibition of histone deacetylases 3 (HDAC3) being linked to increased osteogenic differentiation. This study aimed to induce epigenetic reprogramming using the HDAC2 and 3 selective inhibitor, MI192 to promote hDPSCs osteogenic capacity for bone regeneration. MI192 treatment caused a time–dose-dependent change in hDPSC morphology and reduction in viability. Additionally, MI192 successfully augmented hDPSC epigenetic functionality, which resulted in increased histone acetylation and cell cycle arrest at the G2/M phase. MI192 pre-treatment exhibited a dose-dependent effect on hDPSCs alkaline phosphatase activity. Quantitative PCR and In-Cell Western further demonstrated that MI192 pre-treatment significantly upregulated hDPSCs osteoblast-related gene and protein expression (alkaline phosphatase, bone morphogenic protein 2, type I collagen and osteocalcin) during osteogenic differentiation. Importantly, MI192 pre-treatment significantly increased hDPSCs extracellular matrix collagen production and mineralisation. As such, for the first time, our findings show that epigenetic reprogramming with the HDAC2 and 3 selective inhibitor MI192 accelerates the osteogenic differentiation of hDPSCs, demonstrating the considerable utility of this MSCs engineering approach for bone augmentation strategies.

scholarly journals SAVER: sodium valproate for the epigenetic reprogramming of high-risk oral epithelial dysplasia—a phase II randomised control trial study protocol

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Caroline McCarthy ◽  
Joseph Sacco ◽  
Stefano Fedele ◽  
Michael Ho ◽  
Stephen Porter ◽  
...  
Keyword(s):  
High Risk ◽  
Sodium Valproate ◽  
Study Protocol ◽  
Epigenetic Reprogramming ◽  
Epithelial Dysplasia ◽  
Phase Iii ◽  
Cancer Development ◽  
Randomised Control Trial ◽  
Oral Epithelial Dysplasia ◽  
Oral Epithelial

Abstract Background Sodium valproate (VPA) has been associated with a reduced risk of head and neck cancer development. The potential protective mechanism of action is believed to be via inhibition of histone deacetylase and subsequent epigenetic reprogramming. SAVER is a phase IIb open-label, randomised control trial of VPA as a chemopreventive agent in patients with high-risk oral epithelial dysplasia (OED). The aim of the trial is to gather preliminary evidence of the clinical and biological effects of VPA upon OED and assess the feasibility and acceptability of such a trial, with a view to inform a future definitive phase III study. Methods One hundred and ten patients with high-risk OED will be recruited from up to 10 secondary care sites in the UK and randomised into either VPA or observation only for 4 months. Women of childbearing potential will be excluded due to the teratogenic properties of VPA. Tissue and blood samples will be collected prior to randomisation and on the last day of the intervention/observation-only period (end of 4 months). Clinical measurement and additional safety bloods will be taken at multiple time points during the trial. The primary outcome will be a composite, surrogate endpoint of change in lesion size, change in grade of dysplasia and change in LOH profile at 8 key microsatellite regions. Feasibility outcomes will include recruitment targets, compliance with the study protocol and adverse effects. A qualitative sub-study will explore patient experience and perception of the trial. Discussion The current management options for patients with high-risk OED are limited and mostly include surgical resection and clinical surveillance. However, there remains little evidence whether surgery can effectively lead to a notable reduction in the risk of oral cancer development. Similarly, surveillance is associated with concerns regarding delayed diagnosis of OED progressing to malignancy. The SAVER trial provides an opportunity to investigate the effects of a repurposed, inexpensive and well-tolerated medication as a potential chemopreventive strategy for patients with high-risk OED. The clinical and biological findings of SAVER will inform the appropriateness, design and feasibility of a definitive phase III trial. Trial registration The trial is registered with the European Clinical Trials Database (Eudra-CT 2018-000197-30). (http://www.isrctn.com/ISRCTN12448611). The trial was prospectively registered on 24/04/2018.

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