Electromagnetic Fields Mediate Efficient Cell Reprogramming into a Pluripotent State

Baek, Soonbong; Quan, Xiaoyuan; Kim, Soochan; Lengner, Christopher J.; Park, Jung-Keug; Kim, Jong-Pil

doi:10.1021/nn502923s

Cited by 65 publications

(58 citation statements)

References 41 publications

(61 reference statements)

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“…[5] Baek et al showed that extremely low-frequency electromagnetic field can replace Sox2, Klf4, and c-Myc during reprogramming and enhance reprogramming efficiency. [19] Another recent study found that a grapheme-based substrate can enhance OSKM-induced reprogramming of MEFs by inducing the mesenchymal-to-epithelial transition (MET) and epigenetic dynamics. [20] To date, few studies have investigated how substrate elasticity modulates the reprogramming of somatic cells into iPSCs.…”

Section: Introductionmentioning

confidence: 99%

Stiffness of Hydrogels Regulates Cellular Reprogramming Efficiency Through Mesenchymal‐to‐Epithelial Transition and Stemness Markers

Choi

Park

Kim

et al. 2015

Macromolecular Bioscience

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The stiffness of hydrogels has been reported to direct cell fate. Here, we found that the stiffness of hydrogels promotes the reprogramming of mouse embryonic fibroblasts into induced pluripotent stem cells (iPSCs). We prepared cell culture substrates of various stiffnesses (0.1, 1, 4, 10, and 20 kPa) using a polyacrylamide hydrogel. We found that culture on a soft hydrogel plays an important role in inducing cellular reprogramming into iPSCs via activation of mesenchymal-to-epithelial transition and enhancement of stemness marker expression. These results suggest that physical signals at the interface between cell and substrate can be used as a potent regulator to promote cell fate changes associated with reprogramming into iPSCs, which may lead to effective and reproducible iPSC-production.

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Section: Introductionmentioning

confidence: 99%

Stiffness of Hydrogels Regulates Cellular Reprogramming Efficiency Through Mesenchymal‐to‐Epithelial Transition and Stemness Markers

Choi

Park

Kim

et al. 2015

Macromolecular Bioscience

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“…The potential of ELF-MF exposure to destabilize epigenetic modifications in general and in a cancer-relevant manner has not been addressed systematically. Yet, it was reported to alter global levels of 5mC and the expression of DNA methyltransferases DNMT1 and DNMT3b in murine spermatocyte-derived cells31, and to increase the reprogramming efficiency of somatic cells by upregulation of the histone lysine methyltransferase Mll2, which appears to enrich H3K4me3 at pluripotency genes32.…”

mentioning

confidence: 99%

ELF-MF exposure affects the robustness of epigenetic programming during granulopoiesis

Manser

Sater

Schmid

et al. 2017

Sci Rep

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Extremely-low-frequency magnetic fields (ELF-MF) have been classified as “possibly carcinogenic” to humans on the grounds of an epidemiological association of ELF-MF exposure with an increased risk of childhood leukaemia. Yet, underlying mechanisms have remained obscure. Genome instability seems an unlikely reason as the energy transmitted by ELF-MF is too low to damage DNA and induce cancer-promoting mutations. ELF-MF, however, may perturb the epigenetic code of genomes, which is well-known to be sensitive to environmental conditions and generally deranged in cancers, including leukaemia. We examined the potential of ELF-MF to influence key epigenetic modifications in leukaemic Jurkat cells and in human CD34+ haematopoietic stem cells undergoing in vitro differentiation into the neutrophilic lineage. During granulopoiesis, sensitive genome-wide profiling of multiple replicate experiments did not reveal any statistically significant, ELF-MF-dependent alterations in the patterns of active (H3K4me2) and repressive (H3K27me3) histone marks nor in DNA methylation. However, ELF-MF exposure showed consistent effects on the reproducibility of these histone and DNA modification profiles (replicate variability), which appear to be of a stochastic nature but show preferences for the genomic context. The data indicate that ELF-MF exposure stabilizes active chromatin, particularly during the transition from a repressive to an active state during cell differentiation.

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“…These indicate that the surface modification by SiO 2 might retard this permeation process and lead to smaller Tet molecule density at the bottom surface and smaller scaling factor on the signal induction (see also Figure S2 19 ) although this modification can concentrate the tilted angle by 0. 3 and increase the mean free path by 2.4 lm.…”

Section: Physical Characteristics Of the "Wired" Signal Inductionmentioning

confidence: 95%

“…For example, somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells by defined factors, 1 and 3D cultures can generate cells with stemlike properties in vitro. 2 In addition, external acting fields (e.g., electromagnetic fields 3 and infrared radiation 4 ) can affect cell development and differentiation as well, thanking the rapid and precise responding to signals from environments. In living systems, however, a perfect match between ligands/agonists and receptors may be questioned owing to the relatively low binding probability dominated by molecule collision.…”

Section: Introductionmentioning

confidence: 99%

Observation of “wired” cell communication over 10-μm and 20-μm poly(dimethylsiloxane) barriers in tetracycline inducible expression systems

Kuo

Chi

et al. 2016

Journal of Applied Physics

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Communication between cells and extracellular environments is of interest because of its critical roles in cell development and differentiation. Particularly, this signal transduction is commonly believed to rely on the contact and binding of the participating molecules/proteins, suggesting that the binding distance needed is less than a few nanometers. However, it is difficult to precisely match the rapidly binding interaction which depends on the probability of molecular collision in living systems, raising a hypothesis that another mechanism exists, could promote this signal communication, and remains unknown. Here we report that a long-range signal delivery over 10-μm and 20-μm polydimethylsiloxane (PDMS) barriers can be observed in microfluidically tetracycline (Tet) inducible expression systems. Results show that a significant increment of the long-range induced green fluorescent protein in human embryonic kidney 293T (HEK 293T) cells by the stimulation of Tet is demonstrated, and that such a signal induction is not dominated by Tet diffusion and displays a specific bindingless property. In addition, our experimental results, combined with theoretical modeling, suggest that this communication exhibits a bump-shaped characteristic depending on barrier thickness, materially structural property, surface roughness, and agonist concentration. It strongly relies on the PDMS barrier to delivery signal; therefore, we call such a mechanism as “wired” cell communication instead of wireless. These results could ignite interests in the novel and “wired” cell communication, which we call it X-signal, and in the use of such systems for the study of cellular biology and development of new drug.

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Electromagnetic Fields Mediate Efficient Cell Reprogramming into a Pluripotent State

Cited by 65 publications

References 41 publications

Stiffness of Hydrogels Regulates Cellular Reprogramming Efficiency Through Mesenchymal‐to‐Epithelial Transition and Stemness Markers

Stiffness of Hydrogels Regulates Cellular Reprogramming Efficiency Through Mesenchymal‐to‐Epithelial Transition and Stemness Markers

ELF-MF exposure affects the robustness of epigenetic programming during granulopoiesis

Observation of “wired” cell communication over 10-μm and 20-μm poly(dimethylsiloxane) barriers in tetracycline inducible expression systems

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