Tumor suppressor let-7 acts as a key regulator for pluripotency gene expression in Muse cells

• Published in: Cellular and molecular life sciences : CMLS 2024-12, Vol.81 (1), p.54-54, Article 54
• Main Authors: Li, Gen, Wakao, Shohei, Kitada, Masaaki, Dezawa, Mari
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Alprostadil; antagonists; Biochemistry; Biomedical and Life Sciences; Biomedicine; blood; Bone marrow; Cell Biology; Cell differentiation; Cell self-renewal; Connective tissues; Embryo cells; Embryonic Stem Cells; Gene Expression; Genes; Glycolysis; KLF4 protein; Life Sciences; microRNA; MicroRNAs; miRNA; neoplasms; Oct-4 protein; Original; Original Article; Peripheral blood; Phosphatidylinositol 3-Kinases - genetics; Pluripotency; Proto-Oncogene Proteins c-akt; Ribonucleic acid; risk; RNA; Senescence; Stem cells; Surface markers; Tumor suppressor genes; Tumorigenicity; Tumors
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-023-05089-9

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.