Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Acceleration of Mesenchymal-to-Epithelial Transition (MET) during Direct Reprogramming Using Natural Compounds

  • Seo, Ji-Hye (Department of Dental Pharmacology, School of Dentistry, Jeonbuk National University) ;
  • Jang, Si Won (Department of Agricultural Convergence Technology, Jeonbuk National University) ;
  • Jeon, Young-Joo (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Eun, So Young (Musculoskeletal and Immune Disease Research Institute School of Medicine, Wonkwang University) ;
  • Hong, Yean Ju (Department of Psychiatry and Molecular Neurobiology Laboratory, McLean Hospital and Program in Neuroscience, Harvard Medical School) ;
  • Do, Jeong Tae (Department of Stem Cell and Regenerative Biotechnology, KU Institute of Science and Technology, Konkuk University) ;
  • Chae, Jung-il (Department of Dental Pharmacology, School of Dentistry, Jeonbuk National University) ;
  • Choi, Hyun Woo (Department of Agricultural Convergence Technology, Jeonbuk National University)
  • Received : 2022.08.30
  • Accepted : 2022.09.13
  • Published : 2022.10.28
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Abstract

Induced pluripotent stem cells (iPSCs) can be generated from somatic cells using Oct4, Sox2, Klf4, and c-Myc (OSKM). Small molecules can enhance reprogramming. Licochalcone D (LCD), a flavonoid compound present mainly in the roots of Glycyrrhiza inflata, acts on known signaling pathways involved in transcriptional activity and signal transduction, including the PGC1-α and MAPK families. In this study, we demonstrated that LCD improved reprogramming efficiency. LCD-treated iPSCs (LCD-iPSCs) expressed pluripotency-related genes Oct4, Sox2, Nanog, and Prdm14. Moreover, LCD-iPSCs differentiated into all three germ layers in vitro and formed chimeras. The mesenchymal-to-epithelial transition (MET) is critical for somatic cell reprogramming. We found that the expression levels of mesenchymal genes (Snail2 and Twist) decreased and those of epithelial genes (DSP, Cldn3, Crb3, and Ocln) dramatically increased in OR-MEF (OG2+/+/ROSA26+/+) cells treated with LCD for 3 days, indicating that MET effectively occurred in LCD-treated OR-MEF cells. Thus, LCD enhanced the generation of iPSCs from somatic cells by promoting MET at the early stages of reprogramming.

Keywords

Acknowledgement

This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R111A1A01048981) and the Korea government (MSIP; Ministry of Science, ICT & Future Planning) (NRF-2017R1C1B5077043).

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