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BackgroundPhosphoinositide-3 kinase (PI3K)/AKT signaling participates in cellular proliferation, survival and tumorigenesis. The activation of AKT signaling promotes the cellular reprogramming including generation of induced pluripotent stem cells (iPSCs) and dedifferentiation of primordial germ cells (PGCs). Previous studies suggested that AKT promotes reprogramming by activating proliferation and glycolysis. Here we report a line of evidence that supports the notion that AKT signaling is involved in TET-mediated DNA demethylation during iPSC induction.MethodsAKT signaling was activated in mouse embryonic fibroblasts (MEFs) that were transduced with OCT4, SOX2 and KLF4. Multiomics analyses were conducted in this system to examine the effects of AKT activation on cells undergoing reprogramming.ResultsWe revealed that cells undergoing reprogramming with artificially activated AKT exhibit enhanced anabolic glucose metabolism and accordingly increased level of cytosolic α-ketoglutarate (αKG), which is an essential cofactor for the enzymatic activity of the 5-methylcytosine (5mC) dioxygenase TET. Additionally, the level of TET is upregulated. Consistent with the upregulation of αKG production and TET, we observed a genome-wide increase in 5-hydroxymethylcytosine (5hmC), which is an intermediate in DNA demethylation. Moreover, the DNA methylation level of ES-cell super-enhancers of pluripotency-related genes is significantly decreased, leading to the upregulation of associated genes. Finally, the transduction of TET and the administration of cell-permeable αKG to somatic cells synergistically enhance cell reprogramming by Yamanaka factors.ConclusionThese results suggest the possibility that the activation of AKT during somatic cell reprogramming promotes epigenetic reprogramming through the hyperactivation of TET at the transcriptional and catalytic levels.

Phosphoinositide-3 kinase (PI3K)/AKT signaling participates in cellular proliferation, survival, and tumorigenesis as well as cellular reprogramming including generation of induced pluripotent stem cells (iPSCs). In this study, we revealed that activation of AKT in somatic cells undergoing reprogramming enhances epigenetic reprogramming. Activated AKT in reprogramming cells triggers elevated anabolic glucose metabolism, and, accordingly, increases the level of α-ketoglutarate (αKG) which is an essential cofactor for the enzymatic activity of the 5-methylcytosine (5mC) dioxygenase TET. Additionally, the level of TET was upregulated. Consistent with upregulated αKG production and TET, we observed a genome-wide increase in 5-hydorxymethylcytosine (5hmC) which is an intermediate in the DNA demethylation process. Moreover, DNA methylation level at ES-cell super-enhancers of pluripotency-related genes was significantly decreased, leading upregulation of associated genes. Taken together, our results indicate that AKT signaling is associated with epigenetic regulation by hyperactivating TET at catalytical and transcriptional levels during the somatic cell reprogramming.

1. Introduction For the expansion of application fields (ex. tailor-made photocatalysts and high-efficiency laser) of semiconductor, novel semiconductor materials with variable optical gaps in the range from 1.2 to 3.0 eV is necessary to be developed. The promising candidate of these semiconductor is carbon-rich amorphous silicon-carbon alloy (C-rich a-SiC).[1] The optical gaps (Eog) of C-rich a-SiC can be changed from 1.2 to 2.7 eV by changing the Si/C ratio. Hetero-junction solar cell comprising N-doped C-rich a-SiC with Eog = 2.7 eV and p-type Si have been reported to show the function of photon to electron conversion.[2] However, solar cells comprising N-doped C-rich a-SiC with Eog from 1.2 to 1.7 eV showed extremely lower conversion efficiencies. Therefore, all of these C-rich a-SiC with Eog from 1.2 to 2.7 eV may not be applied to photoelectronic devices. The objective of this study is to realize C-rich a-SiC with lower Eog (frim 1.2 to 1.7 eV) that have higher semiconductor property and are able to be applied to photoelectronic devices. a-SiC has a multiphase structure in which amorphous Si-C network (Si:C = x:1-x), sp2-hybridized carbon cluster (sp 2 clusters), and silicon-like clusters (Si-cluster) coexist. It has been reported that excess sp2 cluster worked as a recombination center of photoexcited carries. It results in the degradation of efficiencies of photon to electron conversion. In order to realize C-rich a-SiC with lower Eog and higher photon to electron conversion efficiency, the synthesis method that can enhance of ratio of C/Si in amorphous Si-C network and suppress the formation of sp 2 clusters in C-rich a-SiC is necessary to be developed. In this study, CVD synthesis using high-frequency and lower power r. f. plasma was tried to be adopted to induce two types of structural change at C-rich a-SiC. High-frequency and lower power r. f. plasma can avoid the formation of sp 2 clusters in C-rich a-SiC. It results in the semiconductor materials with lower Eog and higher photon to electron conversion efficiency. 2. Experimental Nitrogen-doped C-rich a-SiC thin films were synthesized by radio frequency plasma enhanced chemical vapor deposition system (RF-PeCVD) (13.56 MHz, SAMCO Co., Ltd. Model BPD-1) using tetramethylsilane, 1,1,3,3-tetrametyldisilazane and n-hexanes as source materials. C-rich a-SiC thin films were deposited on glass plate and boron-doped silicon (100) substrate (resistivity of 2 W cm) after an in-situ sputter cleaning with argon ions. Substrate temperature was kept at 160 degree C during CVD deposition. The frequency of r.f. power supply was set at 60 MHz and r.f power were changed from 5 to 26 W. The deposition time was 80 minutes. Transmission spectra of N-doped C-rich a-SiC deposited on glass substrates were examined by UV-Vis spectrophotometer (JASCO Co., Ltd. V-670). The performance of heterojunction solar cells was investigated by current-voltage (I-V) measurement (KEYSIGHT, B2901A) with simulated AM 1.5 sunlight (ASAHI SPECTRA, HAL-320). 3. Results and Discussion Eog estimated from transmission spectra (Fig. 1) of resulting N-doped C-rich a-SiC were found to be in the range from 1.40 to 2.96 eV, as shown in Table 1. Eog was able to be controlled to lower value (1.4 eV) thorough the change of the S/C ratios in C-rich a-SiC (by changing the volume ratio of n-hexane in source materials). All hetero-junction solar cells comprising N-doped C-rich a-SiC with various Eog and p-type Si crystal were confirmed to show the function of photon-to electron conversion (Table 1). The improvement of function of photon to electron conversion at C-rich a-SiC with lower Eog (ca. 1.4 eV) might be caused by the suppression of the recombination of photo-exited electrons and holes. In Figure 1, the absorption peak of sp 2 clusters was observed at 1.1 eV and was clearly separated from the absorption peak of amorphous Si-C network (observed at 2.6 eV). The intensity decrease and peak shift to lower energy side of the absorption of sp 2 clusters in Fig. 1 indicates the decrease of the amount of sp 2 clusters and the enlargement of size of sp 2 clusters. These structural change might cause the suppression of recombination of photo-carriers. The relation between Eog and open circuit voltage of solar cell was consistent with estimated value from electronic structure of C-rich a-SiC. It was summarized that the development of C-rich a-SiC semiconductors with lower Eog (in the range from 1.4 to 1.7 eV) that are able to be applied to photo-electronic devices was successfully achieved. 4. References [1] K. Honda et al., ECS J. Solid State Sci. Technol. 5, 590 (2006). [2] H. Naragino et al., ECS Trans. 75, 153 (2016). Figure 1

Amorphous carbon (a-C) based catalysts having higher activity and stability for oxygen reduction reaction (ORR) were achieved by introducing quinone and carboxy groups onto a-C surfaces. The surface-bonded quinone groups increased the rate of ORR to hydrogen peroxide. The surface carboxy groups promoted the activity toward electrochemical peroxide reduction. However, few studies have reported on their contribution. ORR activity was controlled by varying density of quinone and carboxy groups on the a-C surfaces. The ORR activity was proceeded by 2 + 2 electron mechanism through H2O2 that acted as an intermediate. The number of electrons transferred per O2 molecule reached 4.08 at a maximum. The catalytic activity of the catalyst was stable in long term measurements (150 times in 20 h) because a-C inherently has high corrosion resistance and oxygen-contained surface functionalities are stable in aqueous solution. Consequently, the a-C catalysts possessed high ORR reproducibility.