• Title/Summary/Keyword: Epigenetic reprogramming

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Epigenetic Reprogramming in Cloned Embryos

  • Kang, Yong-Kook;Han, Yong-Mahn;Lee, Kyung-Kwang
    • Proceedings of the KSAR Conference
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    • 2001.10a
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    • pp.25-31
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    • 2001
  • During early development, a dramatic reduction in methylation levels occurs in mouse (Monk et al., 1987). The process of epigenetic reprogramming in early embryos erases gamete-specific methylation patterns inherited from the parents (Howlett & Reik 1991, Monk et al., 1987, Oswald et al., 2000, Sanford et al., 1984). This genome-wide demethylation process may be a prerequisite for the formation of pluripotent stem cells that are important for the later development (Reik & Surani 1997). During post-implantation development, a wave of de novo methylation takes place; most of the genomic DNA is methylated at defined developmental timepoints, whereas tissue-specific genes undergo demethylation in their tissues of expression (Kafri et al., 1992, Razin & Kafri 1994). Another demethylation-remethylation cycle of epigenetic reprogramming takes place during gametogenesis and is necessary for resetting of genomic imprinting (Solter 1988). The dynamic epigenetic reprogramming events appear to be basic and are probably conserved in eutherian mammals (see below). (omitted)

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Epigenetic Reprogramming and Cloning (후성 유전학적 리프로그래밍과 클로닝)

  • Han Yong-Mahn;Kang Yong-Kook;Koo Deog-Bon;Lee Kyung-Kwang
    • Development and Reproduction
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    • v.7 no.2
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    • pp.61-68
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    • 2003
  • Zygote genome should entail a complex process of epigenetic reprogramming including a global DNA demethylation to reach a totipotency or pluripotency during early mammalian development. In this study, we have analyzed methylation patterns in cloned bovine embryos to monitor the epigenetic reprogramming process of donor genomic DNA. Aberrant DNA methylation patterns were observed in various genomic regions of cloned embryos except single-copy gene sequences. The overall genomic methylation status of cloned embryos was quite different from that of normal embryos produced in viかo or in vivo. Abnormal methylation profiles were also specifically represented in trophectoderm cells of cloned embryos, which probably result in widespread gene dysregulation in extraembryonic region or placental dysfunction familiar to cloned animals. Our findings suggest that developmental failures of cloned embryos are due to incomplete epigenetic reprogramming of donor genomic DNA. Understanding the epigenetic reprogramming processes of donor genome will clearly define the faulty development of cloned embryos.

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Metabolic Signaling to Epigenetic Alterations in Cancer

  • Kim, Jung-Ae;Yeom, Young Il
    • Biomolecules & Therapeutics
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    • v.26 no.1
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    • pp.69-80
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    • 2018
  • Cancer cells reprogram cellular metabolism to support the malignant features of tumors, such as rapid growth and proliferation. The cancer promoting effects of metabolic reprogramming are found in many aspects: generating additional energy, providing more anabolic molecules for biosynthesis, and rebalancing cellular redox states in cancer cells. Metabolic pathways are considered the pipelines to supply metabolic cofactors of epigenetic modifiers. In this regard, cancer metabolism, whereby cellular metabolite levels are greatly altered compared to normal levels, is closely associated with cancer epigenetics, which is implicated in many stages of tumorigenesis. In this review, we provide an overview of cancer metabolism and its involvement in epigenetic modifications and suggest that the metabolic adaptation leading to epigenetic changes in cancer cells is an important non-genetic factor for tumor progression, which cooperates with genetic causes. Understanding the interaction of metabolic reprogramming with epigenetics in cancers may help to develop novel or highly improved therapeutic strategies that target cancer metabolism.

Enhanced Green Fluorescent Protein Gene under the Regulation of Human Oct4 Promoter as a Marker to Identify Reprogramming of Human Fibroblasts

  • Heo, Soon-Young;Ahn, Kwang-Sung;Kang, Jee-Hyun;Shim, Ho-Sup
    • Reproductive and Developmental Biology
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    • v.32 no.2
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    • pp.135-140
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    • 2008
  • Recent studies on nuclear transfer and induced pluripotent stem cells have demonstrated that differentiated somatic cells can be returned to the undifferentiated state by reversing their developmental process. These epigenetically reprogrammed somatic cells may again be differentiated into various cell types, and used for cell replacement therapies through autologous transplantation to treat many degenerative diseases. To date, however, reprogramming of somatic cells into undifferentiated cells has been extremely inefficient. Hence, reliable markers to identify the event of reprogramming would assist effective selection of reprogrammed cells. In this study, a transgene construct encoding enhanced green fluorescent protein (EGFP) under the regulation of human Oct4 promoter was developed as a reporter for the reprogramming of somatic cells. Microinjection of the transgene construct into pronuclei of fertilized mouse eggs resulted in the emission of green fluorescence, suggesting that the undifferentiated cytoplasmic environment provided by fertilized eggs induces the expression of EGFP. Next, the transgene construct was introduced into human embryonic fibroblasts, and the nuclei from these cells were transferred into enucleated porcine oocytes. Along with their in vitro development, nuclear transfer embryos emitted green fluorescence, suggesting the reprogramming of donor nuclei in nuclear transfer embryos. The results of the present study demonstrate that expression of the transgene under the regulation of human Oct4 promoter coincides with epigenetic reprogramming, and may be used as a convenient marker that non-invasively reflects reprogramming of somatic cells.

Factors Involving Reprogramming in Cloned Embryos

  • Kim, N. H;X. S. Cui;Kim, I. H.;Y. M. Han
    • Korean Journal of Animal Reproduction
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    • v.27 no.4
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    • pp.349-357
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    • 2003
  • Although nuclear transfer (NT) techniques are used to clone animals, its efficiency is very low. Moreover, nuclear transfer has resulted in offspring with severe developmental problems, probably due to incomplete nuclear reprogramming. Nuclear reprogramming is characterized by functional modification of the transferred nucleus to allow it to direct normal embryo development with the potential to grow to term. Although the nature of the reprogramming factor(s) in mammals is not clear, various nuclear as well as cytoplasmic components are involved in the processes. In this article we review recent data on factors involved in the nuclear reprogramming of cloned embryos.

Cooperative Instruction of Signaling and Metabolic Pathways on the Epigenetic Landscape

  • Kim, Jung-Ae
    • Molecules and Cells
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    • v.41 no.4
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    • pp.264-270
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    • 2018
  • Cells cope with diverse intrinsic and extrinsic stimuli in order to make adaptations for survival. The epigenetic landscape plays a crucial role in cellular adaptation, as it integrates the information generated from stimuli. Signaling pathways induced by stimuli communicate with chromatin to change the epigenetic landscape through regulation of epigenetic modifiers. Metabolic dynamics altered by these stimuli also affect the activity of epigenetic modifiers. Here, I review the current understanding of epigenetic regulation via signaling and metabolic pathways. In addition, I will discuss possible ways to achieve specificity of epigenetic modifications through the cooperation of stimuli-induced signal transduction and metabolic reprogramming.

Dental-derived cells for regenerative medicine: stem cells, cell reprogramming, and transdifferentiation

  • Young-Dan Cho;Kyoung-Hwa Kim;Yong-Moo Lee;Young Ku;Yang-Jo Seol
    • Journal of Periodontal and Implant Science
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    • v.52 no.6
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    • pp.437-454
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    • 2022
  • Embryonic stem cells have been a popular research topic in regenerative medicine owing to their pluripotency and applicability. However, due to the difficulty in harvesting them and their low yield efficiency, advanced cell reprogramming technology has been introduced as an alternative. Dental stem cells have entered the spotlight due to their regenerative potential and their ability to be obtained from biological waste generated after dental treatment. Cell reprogramming, a process of reverting mature somatic cells into stem cells, and transdifferentiation, a direct conversion between different cell types without induction of a pluripotent state, have helped overcome the shortcomings of stem cells and raised interest in their regenerative potential. Furthermore, the potential of these cells to return to their original cell types due to their epigenetic memory has reinforced the need to control the epigenetic background for successful management of cellular differentiation. Herein, we discuss all available sources of dental stem cells, the procedures used to obtain these cells, and their ability to differentiate into the desired cells. We also introduce the concepts of cell reprogramming and transdifferentiation in terms of genetics and epigenetics, including DNA methylation, histone modification, and non-coding RNA. Finally, we discuss a novel therapeutic avenue for using dental-derived cells as stem cells, and explain cell reprogramming and transdifferentiation, which are used in regenerative medicine and tissue engineering.

Ground-State Conditions Promote Robust Prdm14 Reactivation and Maintain an Active Dlk1-Dio3 Region during Reprogramming

  • Habib, Omer;Habib, Gizem;Moon, Sung-Hwan;Hong, Ki-Sung;Do, Jeong Tae;Choi, Youngsok;Chang, Sung Woon;Chung, Hyung-Min
    • Molecules and Cells
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    • v.37 no.1
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    • pp.31-35
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    • 2014
  • Induced pluripotent stem cells (iPSCs) are capable of unlimited self-renewal and can give rise to all three germ layers, thereby providing a new platform with which to study mammalian development and epigenetic reprogramming. However, iPSC generation may result in subtle epigenetic variations, such as the aberrant methylation of the Dlk1-Dio3 locus, among the clones, and this heterogeneity constitutes a major drawback to harnessing the full potential of iPSCs. Vitamin C has recently emerged as a safeguard to ensure the normal imprinting of the Dlk1-Dio3 locus during reprogramming. Here, we show that vitamin C exerts its effect in a manner that is independent of the reprogramming kinetics. Moreover, we demonstrate that reprogramming cells under 2i conditions leads to the early upregulation of Prdm14, which in turn results in a highly homogeneous population of authentic pluripotent colonies and prevents the abnormal silencing of the Dlk1-Dio3 locus.