Molecules and Cells

  • 제46권4호
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  • Pages.209-218
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  • 2023
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Homogeneity of XEN Cells Is Critical for Generation of Chemically Induced Pluripotent Stem Cells

  • Dahee Jeong (Department of Stem Cell Biology, School of Medicine, Konkuk University) ;
  • Yukyeong Lee (Department of Stem Cell Biology, School of Medicine, Konkuk University) ;
  • Seung-Won Lee (Department of Stem Cell Biology, School of Medicine, Konkuk University) ;
  • Seokbeom Ham (Department of Stem Cell Biology, School of Medicine, Konkuk University) ;
  • Minseong Lee (Department of Stem Cell Biology, School of Medicine, Konkuk University) ;
  • Na Young Choi (Department of Stem Cell Biology, School of Medicine, Konkuk University) ;
  • Guangming Wu (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) ;
  • Hans R. Scholer (Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine) ;
  • Kinarm Ko (Department of Stem Cell Biology, School of Medicine, Konkuk University)
  • 투고 : 2022.08.18
  • 심사 : 2022.10.23
  • 발행 : 2023.04.30
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초록

In induced pluripotent stem cells (iPSCs), pluripotency is induced artificially by introducing the transcription factors Oct4, Sox2, Klf4, and c-Myc. When a transgene is introduced using a viral vector, the transgene may be integrated into the host genome and cause a mutation and cancer. No integration occurs when an episomal vector is used, but this method has a limitation in that remnants of the virus or vector remain in the cell, which limits the use of such iPSCs in therapeutic applications. Chemical reprogramming, which relies on treatment with small-molecule compounds to induce pluripotency, can overcome this problem. In this method, reprogramming is induced according to the gene expression pattern of extra-embryonic endoderm (XEN) cells, which are used as an intermediate stage in pluripotency induction. Therefore, iPSCs can be induced only from established XEN cells. We induced XEN cells using small molecules that modulate a signaling pathway and affect epigenetic modifications, and devised a culture method which can produce homogeneous XEN cells. At least 4 passages were required to establish morphologically homogeneous chemically induced XEN (CiXEN) cells, whose properties were similar to those of XEN cells, as revealed through cellular and molecular characterization. Chemically iPSCs derived from CiXEN cells showed characteristics similar to those of mouse embryonic stem cells. Our results show that the homogeneity of CiXEN cells is critical for the efficient induction of pluripotency by chemicals.

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과제정보

This research was supported by National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (NRF-2021R1F1A1057192) and Korea Environment Industry & Technology Institute (KEITI) through Core Technology Development Project for Environmental Diseases Prevention and Management, funded by Korea Ministry of Environment (MOE) (2021003310002).

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