Replacement of Oct4 by Tet1 during iPSC Induction Reveals an Important Role of DNA Methylation and Hydroxymethylation in Reprogramming
Open accessAbstract
DNA methylation and demethylation have been proposed to play an important role in somatic cell reprogramming. Here, we demonstrate that the DNA hydroxylase Tet1 facilitates pluripotent stem cell induction by promoting Oct4 demethylation and reactivation. Moreover, Tet1 (T) can replace Oct4 and initiate somatic cell reprogramming in conjunction with Sox2 (S), Klf4 (K), and c-Myc (M). We established an efficient TSKM secondary reprogramming system and used it to characterize the dynamic profiles of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and gene expression during reprogramming. Our analysis revealed that both 5mC and 5hmC modifications increased at an intermediate stage of the process, correlating with a transition in the transcriptional profile. We also found that 5hmC enrichment is involved in the demethylation and reactivation of genes and regulatory regions that are important for pluripotency. Our data indicate that changes in DNA methylation and hydroxymethylation play important roles in genome-wide epigenetic remodeling during reprogramming.
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Tet1 and Tet2, but not Tet3, were upregulated by OSK.
“Because Tet1 and Tet2, but not Tet3, were upregulated by OSK35,36 (Extended Data Fig. 6a), we tested the effect of knocking down Tet1 or Tet2 (sh-Tet1 or sh-Tet2) using AAV37 in the context of damaged, OSK-treated RGCs (Extended Data Fig. 6b–d).”
From Reprogramming to recover youthful epigenetic information and restore vision (2020) · cites this paper as [36]
In “Tet1 Can Facilitate Traditional iPSC Induction in a Hydroxylase-Dependent Manner” (page unavailable), the paper reports that Tet1 progressively increased in both OSK and OSKM reprogramming and that Tet3 was repressed in iPSCs. It reports early Tet2 upregulation for OSKM, but does not establish Tet2 upregulation by OSK alone. (LLM, conf=0.85)
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Self-citation
- Authors
- Gao, Y., Chen, J., Li, K., Wu, T., Huang, B., Liu, W., Kou, X., Zhang, Y., Huang, H., Jiang, Y., Yao, C., Liu, X., Lu, Z., Xu, Z., Kang, L., Chen, J., Wang, H., Cai, T., & Gao, S.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- National Institute of Biological Sciences, Beijing (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Cai, Tao
- Gao, Shaorong
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 12
- Issue
- 4
- Pages
- 453-469
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2134440878
- Cited by
- 362
- References
- 52
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 13 · 2023: 21 · 2022: 20 · 2021: 25 · 2020: 27 · 2019: 30 · 2018: 29 · 2017: 31 · 2016: 44 · 2015: 37 · 2014: 42 · 2013: 25
- FWCI
- 22.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Research Center for Eco-Environmental Sciences OpenIR (Chinese Academy of Sciences) (submittedVersion)
- Funders
- Lanzhou University
- Directorate for Biological Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- TET1, Oct4, somatic cell reprogramming, induced pluripotent stem cells, DNA methylation, DNA hydroxymethylation, 5-hydroxymethylcytosine, 5-methylcytosine, epigenetic remodeling, pluripotency genes, SOX2, KLF4, c-Myc
- MeSH terms
- Kruppel-Like Factor 4, Animals, Cytosine, DNA-Binding Proteins, Enhancer Elements, Genetic, Models, Biological, Proto-Oncogene Proteins, Transcription, Genetic, Proto-Oncogene Proteins c-myc, Gene Expression Regulation, Developmental, DNA Methylation, 5-Methylcytosine, Octamer Transcription Factor-3, Mice, Kruppel-Like Transcription Factors, Embryonic Stem Cells, SOXB1 Transcription Factors, Induced Pluripotent Stem Cells, Transcriptome, Cellular Reprogramming
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