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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 29, 2021 |
| Title |
AKT signaling promotes epigenetic reprogramming via upregulation of TET and its cofactor, alpha-ketoglutarate during iPSC generation. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 KG 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.
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| Overall design |
mRNA profiles of reprogramming mouse embryonic fibroblasts (MEFs) with or without AKT activation. Cells were sampled 10 days after transduction of reprogramming factors (Oct4, Sox2, Klf4) and AKT-MER (AKT fused with modified estrogen receptor). AKT can be activated by administrating 4-hydroxytamoxifen (4OHT).
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| Contributor(s) |
Sekita Y, Sugiura Y, Matsumoto A, Kawasaki Y, Akasaka K, Konno R, Shimizu M, Ito T, Sugiyama E, Yamazaki T, Kanai E, Nakamura T, Suematsu M, Ishino F, Kodera Y, Kohda T, Kimura T |
| Citation(s) |
34563253 |
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| Submission date |
Nov 12, 2020 |
| Last update date |
Sep 29, 2021 |
| Contact name |
Yoichi Sekita |
| E-mail(s) |
ysekita@kitasato-u.ac.jp
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| Phone |
+81-42-778-9481
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| Organization name |
Kitasato University School of Science
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| Department |
Biosciences
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| Lab |
Stem Cell Biology
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| Street address |
1-15-1 Kitasato, Minami-ku
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| City |
Sagamihara |
| State/province |
Kanagawa |
| ZIP/Postal code |
252-0373 |
| Country |
Japan |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (6)
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| GSM4905095 |
Reprogramming MEFs_10 dpi_-4OHT_rep1 [iPS1] |
| GSM4905096 |
Reprogramming MEFs_10 dpi_-4OHT_rep2 [iPS2] |
| GSM4905097 |
Reprogramming MEFs_10 dpi_-4OHT_rep3 [iPS3] |
| GSM4905098 |
Reprogramming MEFs_10 dpi_+4OHT_rep1 [iPS4] |
| GSM4905099 |
Reprogramming MEFs_10 dpi_+4OHT_rep2 [iPS5] |
| GSM4905100 |
Reprogramming MEFs_10 dpi_+4OHT_rep3 [iPS6] |
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| Relations |
| BioProject |
PRJNA677932 |
| SRA |
SRP292322 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE161344_Akt_iPS_scaledTPM_by_Salmon_.csv.gz |
1.4 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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