Mesenchymal to embryonic incomplete transition of human cells by chimeric OCT4/3 (POU5F1) with physiological co-activator EWS

Hatsune Makino, Masashi Toyoda, Kenji Matsumoto, Hirohisa Saito, Koichiro Nishino, Yoshihiro Fukawatase, Masakazu Machida, Hidenori Akutsu, Taro Uyama, Yoshitaka Miyagawa, Hajime Okita, Nobutaka Kiyokawa, Takashi Fujino, Yuichi Ishikawa, Takuro Nakamura, Akihiro Umezawa

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44 Citations (Scopus)

Abstract

POU5F1 (more commonly known as OCT4/3) is one of the stem cell markers, and affects direction of differentiation in embryonic stem cells. To investigate whether cells of mesenchymal origin acquire embryonic phenotypes, we generated human cells of mesodermal origin with overexpression of the chimeric OCT4/3 gene with physiological co-activator EWS (product of the EWSR1 gene), which is driven by the potent EWS promoter by translocation. The cells expressed embryonic stem cell genes such as NANOG, lost mesenchymal phenotypes, and exhibited embryonal stem cell-like alveolar structures when implanted into the subcutaneous tissue of immunodeficient mice. Hierarchical analysis by microchip analysis and cell surface analysis revealed that the cells are subcategorized into the group of human embryonic stem cells and embryonal carcinoma cells. These results imply that cells of mesenchymal origin can be traced back to cells of embryonic phenotype by the OCT4/3 gene in collaboration with the potent cis-regulatory element and the fused co-activator. The cells generated in this study with overexpression of chimeric OCT4/3 provide us with insight into cell plasticity involving OCT4/3 that is essential for embryonic cell maintenance, and the complexity required for changing cellular identity.

Original languageEnglish
Pages (from-to)2727-2740
Number of pages14
JournalExperimental Cell Research
Volume315
Issue number16
DOIs
Publication statusPublished - 2009 Oct 1
Externally publishedYes

Keywords

  • Dedifferentiation
  • Embryonic carcinoma
  • Mesoderm
  • OCT4/3
  • Stem cell
  • iPS cell

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Makino, H., Toyoda, M., Matsumoto, K., Saito, H., Nishino, K., Fukawatase, Y., Machida, M., Akutsu, H., Uyama, T., Miyagawa, Y., Okita, H., Kiyokawa, N., Fujino, T., Ishikawa, Y., Nakamura, T., & Umezawa, A. (2009). Mesenchymal to embryonic incomplete transition of human cells by chimeric OCT4/3 (POU5F1) with physiological co-activator EWS. Experimental Cell Research, 315(16), 2727-2740. https://doi.org/10.1016/j.yexcr.2009.06.016