Mesenchymal to embryonic incomplete transition of human cells by chimeric OCT4/3 (POU5F1) with physiological co-activator EWS.
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.
Makino
Hatsune
H
Department of Reproductive Biology, National Institute for Child Health and Development, Tokyo, 157-8535, Japan.
Toyoda
Masashi
M
Matsumoto
Kenji
K
Saito
Hirohisa
H
Nishino
Koichiro
K
Fukawatase
Yoshihiro
Y
Machida
Masakazu
M
Akutsu
Hidenori
H
Uyama
Taro
T
Miyagawa
Yoshitaka
Y
Okita
Hajime
H
Kiyokawa
Nobutaka
N
Fujino
Takashi
T
Ishikawa
Yuichi
Y
Nakamura
Takuro
T
Umezawa
Akihiro
A
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007621:Karyotyping; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009024:Morphogenesis / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D025341:Principal Component Analysis; D034802:RNA-Binding Protein EWS / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013724:Teratoma / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D034802:RNA-Binding Protein EWS; D011993:Recombinant Fusion Proteins