Induced Pluripotent Stem Cells: Emerging Techniques for Nuclear Reprogramming

Han, Ji Yun; Yoon, Young Sup

doi:10.1089/ars.2010.3814

Cited by 33 publications

(25 citation statements)

References 220 publications

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“…For example, miR-302/367 promotes cellular reprogramming and production of induced pluripotent stem cells (iPSCs) (Lipchina, Studer & Betel, 2012). miRNA clusters can even replace TFs such as octamer-binding transcription factor 4 (OCT4), SRY-box 2 (SOX2), krüppel-like factor 4 (KLF4) and MYC which are commonly used in stem cell manipulation (Han & Yoon, 2011). Thus, miRNA clusters can be utilized for cellular pluripotency and programming.…”

Section: (11) Cellular Reprogrammingmentioning

confidence: 99%

Clustered miRNAs and their role in biological functions and diseases

et al. 2018

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MicroRNAs (miRNAs) are endogenous, small non-coding RNAs known to regulate expression of protein-coding genes. A large proportion of miRNAs are highly conserved, localized as clusters in the genome, transcribed together from physically adjacent miRNAs and show similar expression profiles. Since a single miRNA can target multiple genes and miRNA clusters contain multiple miRNAs, it is important to understand their regulation, effects and various biological functions. Like protein-coding genes, miRNA clusters are also regulated by genetic and epigenetic events. These clusters can potentially regulate every aspect of cellular function including growth, proliferation, differentiation, development, metabolism, infection, immunity, cell death, organellar biogenesis, messenger signalling, DNA repair and self-renewal, among others. Dysregulation of miRNA clusters leading to altered biological functions is key to the pathogenesis of many diseases including carcinogenesis. Here, we review recent advances in miRNA cluster research and discuss their regulation and biological functions in pathological conditions.

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Section: (11) Cellular Reprogrammingmentioning

confidence: 99%

Clustered miRNAs and their role in biological functions and diseases

et al. 2018

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“…Induced pluripotent stem cells share many of the properties of ESC, both advantageous and deleterious. Patient‐specific iPSC are often derived by reprogramming somatic cells using retroviral or lentiviral vectors 50, thus avoiding ethical challenges associated with destruction of human embryos. The most common method of generating iPSC utilizes vectors that integrate into the genomes of reprogrammed cells and thereby become a lasting, problematic source of variation and unpredictability.…”

Section: Challenges Of Using Stem Cells For Organ Engineeringmentioning

confidence: 99%

Organ engineering – combining stem cells, biomaterials, and bioreactors to produce bioengineered organs for transplantation

2012

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Often the only treatment available for patients suffering from diseased and injured organs is whole organ transplant. However, there is a severe shortage of donor organs for transplantation. The goal of organ engineering is to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Recent progress in stem cell biology, biomaterials, and processes such as organ decellularization and electrospinning has resulted in the generation of bioengineered blood vessels, heart valves, livers, kidneys, bladders, and airways. Future advances that may have a significant impact for the field include safe methods to reprogram a patient's own cells to directly differentiate into functional replacement cell types. The subsequent combination of these cells with natural, synthetic and/or decellularized organ materials to generate functional tissue substitutes is a real possibility. This essay reviews the current progress, developments, and challenges facing researchers in their goal to create replacement tissues and organs for patients.

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“…iPSCs are a promising cell source for regenerative biology and appear to be similar to ESCs in terms of proliferation and differentiation capacity [1, 4]. Therefore, iPSCs hold great promise for not only basic stem cell biology but also regenerative medicine, which aims to differentiate patient‐specific iPSC lines into any cell lineage (e.g., neurons and cardiomyocytes) for a wide range of therapeutic applications [6–10].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-302 Increases Reprogramming Efficiency via Repression of NR2F2

et al. 2013

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MicroRNAs (miRNAs) have emerged as critical regulators of gene expression through translational inhibition and RNA decay, and have been implicated in the regulation of cellular differentiation, proliferation, angiogenesis, and apoptosis. In this study, we use global bioinformatics analysis of miRNA and mRNA microarrays to predict novel miRNA-mRNA interactions in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). In particular, we demonstrate a regulatory feedback loop between the miR-302 cluster and two transcription factors, NR2F2 and OCT4. Our data show high expression of miR-302 and OCT4 in pluripotent cells, while NR2F2 is expressed exclusively in differentiated cells. Target analysis predicts that NR2F2 is a direct target of the miR-302, which we experimentally confirm by reporter luciferase assays and real-time PCR. We also demonstrate that NR2F2 directly inhibits the activity of the OCT4 promoter and thus diminishes the positive feedback loop between OCT4 and the miR-302. Importantly, higher reprogramming efficiencies were obtained when we reprogrammed human adipose-derived stem cells (hASCs) into iPSCs using four factors (KLF4, C-MYC, OCT4, and SOX2) plus miR-302 (this reprogramming cocktail is hereafter referred to as “KMOS3”) when compared to using four factors (“KMOS”). Furthermore, shRNA knockdown of NR2F2 mimics the over-expression of miR-302 by also enhancing reprogramming efficiency. Interestingly, we were unable to generate iPSCs from miR-302a/b/c/d alone, which is in contrast to previous publications that have reported that miR-302 by itself can reprogram human skin cancer cells and human hair follicle cells. Taken together, these findings demonstrate that miR-302 inhibits NR2F2 and promotes pluripotency through indirect positive regulation of OCT4. This feedback loop represents an important new mechanism for understanding and inducing pluripotency in somatic cells.

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Induced Pluripotent Stem Cells: Emerging Techniques for Nuclear Reprogramming

Cited by 33 publications

References 220 publications

Clustered miRNAs and their role in biological functions and diseases

Clustered miRNAs and their role in biological functions and diseases

Organ engineering – combining stem cells, biomaterials, and bioreactors to produce bioengineered organs for transplantation

MicroRNA-302 Increases Reprogramming Efficiency via Repression of NR2F2

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