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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (2): 420-424. doi: 10.19723/j.issn.1671-167X.2021.02.032

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Roles of ten eleven translocation proteins family and 5-hydroxymethylcytosine in epigenetic regulation of stem cells and regenerative medicine

ZHAO Jian-fang1,2,LI Dong1,AN Yang1,Δ()   

  1. 1. Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, China
    2. Department of Plastic Surgery and Burns, Peking University First Hospital, Beijing 100034, China
  • Received:2019-03-18 Online:2021-04-18 Published:2021-04-21
  • Contact: Yang AN E-mail:anyangdoctor@163.com

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Abstract:

The methylation of cytosine is one of the most fundamental epigenetic modifications in mammalian genomes, and is involved in multiple crucial processes including gene expression, cell differentiation, embryo development and oncogenesis. In the past, DNA methylation was thought to be an irreversible process, which could only be diluted passively through DNA replication. It is now becoming increa-singly obvious that DNA demethylation can be an active process and plays a crucial role in biological processes. Ten eleven translocation (TET) proteins are the key factors modulating DNA demethylation. This family contains three members: TET1, TET2 and TET3. Although three TET proteins have relatively conserved catalytic domains, their roles in organisms are not repeated, and their expression has significant cell/organ specificity. TET1 is mainly expressed in embryonic stem cells, TET2 is mainly expressed in hematopoietic system, and TET3 is widely expressed in cerebellum, cortex and hippocampus. This family catalyzes 5-methylcytosine to 5-hydroxymethylcytosine and other oxidative products, reactivates silenced-gene expression, in turn maintains stem cell pluripotency and regulates lineage specification. With the development of tissue engineering, organ transplantation, autologous tissue transplantation and artificial prosthesis have been widely used in clinical treatment, but these technologies have limitations. Regenerative medicine, which uses stem cells and stem cell related factors for treatment, may provide alternative therapeutic strategies for multiple diseases. Among all kinds of human stem cells, adipose-derived stem cells (ADSCs) are the most prospective stem cell lineage since they have no ethical issues and can be easily obtained with large quantities. To date, ADSCs have been shown to have strong proli-feration capacity, secrete numerous soluble factors and have multipotent differentiation ability. However, the underlying mechanism of the proliferation, secretion, acquired pluripotency, and lineage specific differentiation of ADSCs are still largely unknown. Some studies have explored the role of epigenetic regulation and TET protein in embryonic stem cells, but little is known about its role in ADSCs. By studying the roles of TET proteins and 5-hydroxymethylcytosine in ADSCs, we could provide new theoretical foundation for the clinical application of ADSCs and the stem cell-based therapy. In the future, combined with bioprinting technology, ADSCs may be used in tissue and organ regeneration, plastic surgery reconstruction and other broader fields.

Key words: Ten eleven translocation protein, 5-hydroxymethylcytosine, Adipose-derived stem cell, Regenerative medicine

CLC Number: 

  • R622

Figure 1

Structure domain of TET protein The carboxyl terminal core catalytic domain is highly conserved in all TET family members and consists of double-stranded β-helix domain and Cys-rich domain. The double-stranded β-helix domain contains binding sites of α-ketoglutaric acid and Fe2+. TET, ten eleven translocation protein."

Figure 2

Role of TET protein in passive and active DNA demethylation TET protein oxidizes 5mC into 5hmc, 5fC and 5caC, of which 5fC and 5caC are directly removed by thymine-DNA glycosylase. Through base excision repair, the resulting base sites are replaced by unmethylated cytosine. TET, ten eleven translocation protein; 5mC, 5-methylcytosine; 5hmC, 5-hydroxymethylcytosine; 5fC, 5-formylcytosine; 5caC, 5-carboxylcytosine."

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