Format

Send to

Choose Destination
See comment in PubMed Commons below
Stem Cell Reports. 2016 Jul 12;7(1):43-54. doi: 10.1016/j.stemcr.2016.05.014. Epub 2016 Jun 30.

Regulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family.

Author information

1
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
2
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA; Department of Cell Biology, Second Military Medical University, Shanghai 200433, P.R. China.
3
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA; Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.
4
Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 Northeast, 10th Street, Oklahoma City, OK 73104, USA.
5
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA; Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, 515041, P.R. China.
6
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA; Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul 135-081, Republic of Korea.
7
Department of Cell Biology, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
8
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA. Electronic address: inhyun.park@yale.edu.

Abstract

Reprogramming to pluripotency after overexpression of OCT4, SOX2, KLF4, and MYC is accompanied by global genomic and epigenomic changes. Histone modification and DNA methylation states in induced pluripotent stem cells (iPSCs) have been shown to be highly similar to embryonic stem cells (ESCs). However, epigenetic differences still exist between iPSCs and ESCs. In particular, aberrant DNA methylation states found in iPSCs are a major concern when using iPSCs in a clinical setting. Thus, it is critical to find factors that regulate DNA methylation states in reprogramming. Here, we found that the miR-29 family is an important epigenetic regulator during human somatic cell reprogramming. Our global DNA methylation and hydroxymethylation analysis shows that DNA demethylation is a major event mediated by miR-29a depletion during early reprogramming, and that iPSCs derived from miR-29a depletion are epigenetically closer to ESCs. Our findings uncover an important miRNA-based approach to generate clinically robust iPSCs.

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center