Review Epigenetic mechanisms of induced pluripotency

Gladych, Marta; Andrzejewska, Anastazja; Oleksiewicz, Urszula; Estécio, Marcos R.H.

doi:10.5114/wo.2014.47135

Cited by 17 publications

(20 citation statements)

References 111 publications

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“…Several studies have shown that the epigenetic landscape of a cell is drastically remodeled during reprogramming enabling the transcription of pluripotency-associated and the repression of differentiation-promoting genes [reviewed in (59)]. There are a number of studies which display a connection between miRNAs and epigenetic modifiers further proving the versatility of miRNAs.…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 98%

Function and significance of MicroRNAs in benign and malignant human stem cells

Utikal

Abba

Novak

et al. 2015

Seminars in Cancer Biology

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Section: Induced Pluripotent Stem Cellsmentioning

confidence: 98%

Function and significance of MicroRNAs in benign and malignant human stem cells

Utikal

Abba

Novak

et al. 2015

Seminars in Cancer Biology

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“…The methylation is established by de novo methyltransferases Dnmt3a and Dmnt3b and preserved by the maintenance methyltransferase Dnmt1 ( Smith & Meissner, 2013 ). During reprogramming, the methylation marks are removed from these endogenous pluripotency genes to allow for their transcription, and tissue-specific genes are hypermethylated ( Gladych et al, 2015 ; Berdasco & Estellar, 2011 ). Indeed, manipulation of the DNA and chromatin modifications by certain small molecules can significantly improve iPSC formation ( Huangfu et al, 2008a , 2008b ; Li et al, 2009b ; Feldman et al, 2006 ) (see reprogramming factors–epigenetic modifiers).…”

Section: Molecular Mechanism Of Induced Pluripotencymentioning

confidence: 99%

“…The bivalent domains are almost exclusively found in pluripotent stem cells, and their restoration represents a vital step in the reprogramming process. During reprogramming, repressive H3K9me3 marks present on the endogenous pluripotency genes (Oct4, Sox2, and Nanog) are gradually replaced by the transcriptionally active H3K4me3 ( Gladych et al, 2015 ). The loss of the H3K9me3 marks allows access of OSKM transgenes to their target regions thus activating the autoregulatory loop.…”

Section: Molecular Mechanism Of Induced Pluripotencymentioning

confidence: 99%

Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications

Omole

Fakoya

2018

PeerJ

151

105

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The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers to reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSC generation. Distinct barriers and enhancers of reprogramming have been elucidated, and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSC field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling, drug discovery and regenerative medicine. Additionally, this study appraises the role of genomic editing technology in the generation of healthy iPSCs.

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“…Somatic cell reprogramming to induced pluripotent stem cells is also dependent on massive alterations within the epigenomic profile of the cells [7,8]. Successful reprogramming reversely mirrors early developmental processes and requires the elimination of epigenetic barriers [9,10] to acquire open chromatin state that is characteristic to stem cells [8,11]. The maintenance of the epigenome becomes more error-prone with age, thus leading to so-called "epigenetic drift"-accumulation of epigenomic aberrations.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Signatures of the Epigenome: Friend or Foe?

Machnik

Oleksiewicz

2020

Cells

Self Cite

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Highly dynamic epigenetic signaling is influenced mainly by (micro)environmental stimuli and genetic factors. The exact mechanisms affecting particular epigenomic patterns differ dependently on the context. In the current review, we focus on the causes and effects of the dynamic signatures of the human epigenome as evaluated with the high-throughput profiling data and single-gene approaches. We will discuss three different aspects of phenotypic outcomes occurring as a consequence of epigenetics interplaying with genotype and environment. The first issue is related to the cases of environmental impacts on epigenetic profile, and its adverse and advantageous effects related to human health and evolutionary adaptation. The next topic will present a model of the interwoven co-evolution of genetic and epigenetic patterns exemplified with transposable elements (TEs) and their epigenetic repressors Krüppel-associated box zinc finger proteins (KRAB–ZNFs). The third aspect concentrates on the mitosis-based microevolution that takes place during carcinogenesis, leading to clonal diversity and expansion of tumor cells. The whole picture of epigenome plasticity and its role in distinct biological processes is still incomplete. However, accumulating data define epigenomic dynamics as an essential co-factor driving adaptation at the cellular and inter-species levels with a benefit or disadvantage to the host.

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Review Epigenetic mechanisms of induced pluripotency

Cited by 17 publications

References 111 publications

Function and significance of MicroRNAs in benign and malignant human stem cells

Function and significance of MicroRNAs in benign and malignant human stem cells

Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications

Dynamic Signatures of the Epigenome: Friend or Foe?

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