Human embryonic stem cells (hESCs) are vulnerable to cell death upon dissociation. Thus, dissociation is an obstacle in culturing, maintaining, and differentiating of hESCs. To date, apoptosis has become the focus of research into the nature of cell death triggered by cellular detachment; it remains baffling whether another form of cell death can occur upon dissociation in hESCs. Here, we demonstrate that iron accumulation and subsequently lipid peroxidation are responsible for dissociation-mediated hESC death. Moreover, we found that a decrease of glutathione peroxidase 4 because of iron accumulation promotes ferroptosis. Inhibition of lipid peroxidation (ferrostatin-1) or chelating iron (deferoxamine) largely suppresses iron accumulation-induced ferroptosis in dissociated hESCs. The results show that P53 mediates the dissociation-induced ferroptosis in hESCs, which is suppressed by pifithrin α. Multiple genes involved in ferroptosis are regulated by the nuclear factor erythroid 2-related factor 2 (Nrf2). In this study, solute carrier family 7 member 11 and glutathione peroxidase 4 are involved in GSH synthesis decreased upon dissociation as a target of Nrf2. In conclusion, our study demonstrates that iron accumulation as a consequence of cytoskeleton disruption appears as a pivotal factor in the initiation of ferroptosis in dissociated hESCs. Nrf2 inhibits ferroptosis via its downstream targets. Our study suggests that the antiferroptotic target might be a good candidate for the maintenance of hESCs.
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http://dx.doi.org/10.1016/j.jbc.2022.101855 | DOI Listing |
Nano Lett
January 2025
Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, South Korea.
Analyzing the cell interface is of paramount importance in understanding how cells interact and communicate with other cells, but an advanced analytical platform that can process complex and networked interactions between cell surface ligands and receptors is lacking. Herein, we developed the cell-interface-deciphering lipid nanotablet (CID-LNT) for multiplexed real-time cell analysis. LNT is a nanoparticle-tethered lipid bilayer chip where freely diffusing plasmonic nanoparticles induce scattering signal changes.
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November 2024
State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
The article explores celery-derived extracellular vesicles (CDEVs), characterized by high cellular uptake, low immunogenicity, and high stability, as a therapeutic strategy for antitumor nanomedicines. The methods employed in this study include cell experiments such as co-culture, Western Blot, and flow cytometry. experiments were conducted in C57BL/6 tumor-bearing mice subcutaneously injected with Lewis lung carcinoma (LLC) cells.
View Article and Find Full Text PDFExtracell Vesicles Circ Nucl Acids
November 2024
The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan 523059, Guangdong, China.
Recent findings have indicated that the deficiency of inhibitory programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9) in pancreatic β-cells is associated with the progression of type 1 diabetes (T1D). This suggests that exogenous PD-L1 and Gal-9 may have promising potential as therapeutics for the treatment of T1D. In light of these reports, a recent work investigated the potential of artificial extracellular vesicles (aEVs) with the presentation of PD-L1 and Gal-9 ligands (PD-L1-Gal-9 aEVs) as a treatment for T1D, with the findings published in .
View Article and Find Full Text PDFiScience
January 2025
School of Life Sciences, Chongqing University, Chongqing 401331, China.
Severe cases of COVID-19 are associated with immune responses that lead to a surge in inflammatory molecules, resulting in multi-organ failure and death. This significant increase in inflammatory factors is triggered by viral proteins. Open reading frame 8 (ORF8) has received particular attention as a unique accessory protein of SARS-CoV-2.
View Article and Find Full Text PDFMater Today Bio
February 2025
Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China.
Sepsis is a serious and life-threatening condition, which can lead to organ failure and death clinically. Abnormally increased cell-free DNA (cfDNA) and inflammatory cytokines are involved in the development and progression of sepsis. Thus, cfDNA clearance and down-regulation of inflammatory factors are essential for the effective treatment of sepsis.
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