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Tumor suppressor let-7 acts as a key regulator for pluripotency gene expression in Muse cells.
Li, Gen; Wakao, Shohei; Kitada, Masaaki; Dezawa, Mari.
Afiliación
  • Li G; Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. gen.li.e6@tohoku.ac.jp.
  • Wakao S; Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
  • Kitada M; Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. Masaaki.Kitada@gmail.com.
  • Dezawa M; Department of Anatomy, Kansai Medical University School of Medicine, 2-5-1 Shin-machi, Hirakata, Osaka, 573-1191, Japan. Masaaki.Kitada@gmail.com.
Cell Mol Life Sci ; 81(1): 54, 2024 Jan 23.
Article en En | MEDLINE | ID: mdl-38261036
ABSTRACT
In embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), the expression of an RNA-binding pluripotency-relevant protein, LIN28, and the absence of its antagonist, the tumor-suppressor microRNA (miRNA) let-7, play a key role in maintaining pluripotency. Muse cells are non-tumorigenic pluripotent-like stem cells residing in the bone marrow, peripheral blood, and organ connective tissues as pluripotent surface marker SSEA-3(+). They express pluripotency genes, differentiate into triploblastic-lineage cells, and self-renew at the single cell level. Muse cells do not express LIN28 but do express let-7 at higher levels than in iPSCs. In Muse cells, we demonstrated that let-7 inhibited the PI3K-AKT pathway, leading to sustainable expression of the key pluripotency regulator KLF4 as well as its downstream genes, POU5F1, SOX2, and NANOG. Let-7 also suppressed proliferation and glycolysis by inhibiting the PI3K-AKT pathway, suggesting its involvement in non-tumorigenicity. Furthermore, the MEK/ERK pathway is not controlled by let-7 and may have a pivotal role in maintaining self-renewal and suppression of senescence. The system found in Muse cells, in which the tumor suppressor let-7, but not LIN28, tunes the expression of pluripotency genes, might be a rational cell system conferring both pluripotency-like properties and a low risk for tumorigenicity.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Alprostadil / Fosfatidilinositol 3-Quinasas Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Alprostadil / Fosfatidilinositol 3-Quinasas Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Japón