13 research outputs found

    Low Cell-Matrix Adhesion Reveals Two Subtypes of Human Pluripotent Stem Cells.

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    We show that a human pluripotent stem cell (hPSC) population cultured on a low-adhesion substrate developed two hPSC subtypes with different colony morphologies: flat and domed. Notably, the dome-like cells showed higher active proliferation capacity and increased several pluripotent genes' expression compared with the flat monolayer cells. We further demonstrated that cell-matrix adhesion mediates the interaction between cell morphology and expression of KLF4 and KLF5 through a serum response factor (SRF)-based regulatory double loop. Our results provide a mechanistic view on the coupling among adhesion, stem cell morphology, and pluripotency, shedding light on the critical role of cell-matrix adhesion in the induction and maintenance of hPSC

    Maintenance of Nucleolar Homeostasis by CBX4 Alleviates Senescence and Osteoarthritis

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    Summary: CBX4, a component of polycomb repressive complex 1 (PRC1), plays important roles in the maintenance of cell identity and organ development through gene silencing. However, whether CBX4 regulates human stem cell homeostasis remains unclear. Here, we demonstrate that CBX4 counteracts human mesenchymal stem cell (hMSC) aging via the maintenance of nucleolar homeostasis. CBX4 protein is downregulated in aged hMSCs, whereas CBX4 knockout in hMSCs results in destabilized nucleolar heterochromatin, enhanced ribosome biogenesis, increased protein translation, and accelerated cellular senescence. CBX4 maintains nucleolar homeostasis by recruiting nucleolar protein fibrillarin (FBL) and heterochromatin protein KRAB-associated protein 1 (KAP1) at nucleolar rDNA, limiting the excessive expression of rRNAs. Overexpression of CBX4 alleviates physiological hMSC aging and attenuates the development of osteoarthritis in mice. Altogether, our findings reveal a critical role of CBX4 in counteracting cellular senescence by maintaining nucleolar homeostasis, providing a potential therapeutic target for aging-associated disorders. : Ren et al. identify a geroprotective role for CBX4 in human mesenchymal stem cells (hMSCs) by maintaining nucleolar homeostasis. Overexpression of CBX4 alleviates hMSC aging and attenuates the development of osteoarthritis, highlighting a potential avenue for the use of CBX4 gene therapy vector in treating aging and aging-related disorders. Keywords: CBX4, stem cell, aging, nucleolus, rDNA, epigenetics, heterochromatin, osteoarthritis, CRISPR/Cas9, gene editin

    Epimedium sempervirens Nakai var. multifoliolatum T. Shimizu

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    原著和名:ソハヤキイカリサウ科名: Berberidaceae = メギ科採集地: 三重県 員弁郡 藤原岳北側の沢 (伊勢 員弁郡 藤原岳北側の沢)採集日: 1990/4/8採集者: 萩庭丈壽整理番号: JH002421国立科学博物館整理番号: TNS-VS-952421備考: 石灰岩
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