GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE161344 Query DataSets for GSE161344
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
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.
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).
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
Submission date Nov 12, 2020
Last update date Sep 29, 2021
Contact name Yoichi Sekita
Phone +81-42-778-9481
Organization name Kitasato University School of Science
Department Biosciences
Lab Stem Cell Biology
Street address 1-15-1 Kitasato, Minami-ku
City Sagamihara
State/province Kanagawa
ZIP/Postal code 252-0373
Country Japan
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (6)
GSM4905095 Reprogramming MEFs_10 dpi_-4OHT_rep1 [iPS1]
GSM4905096 Reprogramming MEFs_10 dpi_-4OHT_rep2 [iPS2]
GSM4905097 Reprogramming MEFs_10 dpi_-4OHT_rep3 [iPS3]
BioProject PRJNA677932
SRA SRP292322

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE161344_Akt_iPS_scaledTPM_by_Salmon_.csv.gz 1.4 Mb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap