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炎症条件下脂肪组织来源间充质干细胞的DNA损伤增加。

Increased DNA damage of adipose tissue-derived mesenchymal stem cells under inflammatory conditions.

作者信息

Páhi Zoltán G, Szűcs Diána, Miklós Vanda, Ördög Nóra, Monostori Tamás, Varga János, Kemény Lajos, Veréb Zoltán, Pankotai Tibor

机构信息

Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Genome Integrity and DNA Repair Core Group, University of Szeged, Szeged, Hungary.

Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.

出版信息

Heliyon. 2024 Aug 20;10(17):e36275. doi: 10.1016/j.heliyon.2024.e36275. eCollection 2024 Sep 15.

DOI:10.1016/j.heliyon.2024.e36275
PMID:39296022
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11407982/
Abstract

Cells have evolved various DNA repair mechanisms to prevent DNA damage from building up. Malfunctions during DNA repair can influence cellular homeostasis because they can bring on genomic instability through the improper recognition of DNA damage or dysregulation of the repair process. Maintaining proper DNA repair is also essential for stem cells (SCs), as they provide a differentiated cell population to the living organism. SCs are regularly used in personalized stem cell therapy. Patients must be treated with specific activators to produce these SCs effectively. This report investigated the impact of treating mesenchymal stem cells (MSC) with lipopolysaccharide, tumor necrosis factor, interferon-gamma, polyinosinic acid, interleukin 1 beta, while monitoring their transcription-related response using next-generation sequencing. RNA sequencing revealed robust gene expression changes, including those of specific genes encoding proteins implicated in DNA damage response. Stem cells can effectively repair specific DNA damages; moreover, they fail to undergo senescence or cell death when genetic lesions accumulate. Here, we draw attention to an elevated DNA repair activation following MSC induction, which may be the main reason for the ineffective stem cell transplantation and may also contribute to the genetic drift that can initiate tumor formation.

摘要

细胞已经进化出各种DNA修复机制,以防止DNA损伤不断累积。DNA修复过程中的故障会影响细胞内稳态,因为它们可能通过对DNA损伤的错误识别或修复过程的失调导致基因组不稳定。维持适当的DNA修复对干细胞(SCs)也至关重要,因为它们为生物体提供分化的细胞群体。干细胞常用于个性化干细胞治疗。必须用特定的激活剂治疗患者才能有效地产生这些干细胞。本报告研究了用脂多糖、肿瘤坏死因子、干扰素-γ、聚肌苷酸、白细胞介素1β处理间充质干细胞(MSC)的影响,同时使用下一代测序监测它们与转录相关的反应。RNA测序揭示了强大的基因表达变化,包括那些编码与DNA损伤反应相关蛋白质的特定基因的变化。干细胞可以有效地修复特定的DNA损伤;此外,当遗传损伤积累时,它们不会衰老或细胞死亡。在这里,我们提请注意间充质干细胞诱导后DNA修复激活的增强,这可能是干细胞移植无效的主要原因,也可能导致引发肿瘤形成的基因漂移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e41/11407982/43a165b98988/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e41/11407982/fb91e65882c0/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e41/11407982/f99a02818fa3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e41/11407982/1570ce4dbfe1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e41/11407982/631123855647/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e41/11407982/43a165b98988/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e41/11407982/fb91e65882c0/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e41/11407982/f99a02818fa3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e41/11407982/1570ce4dbfe1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e41/11407982/631123855647/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e41/11407982/43a165b98988/gr4.jpg

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本文引用的文献

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Front Cell Dev Biol. 2024 Mar 28;12:1367242. doi: 10.3389/fcell.2024.1367242. eCollection 2024.
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Regulation of base excision repair during adipogenesis and osteogenesis of bone marrow-derived mesenchymal stem cells.骨髓间充质干细胞成脂和成骨分化过程中碱基切除修复的调控。
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体外培养平台研究人骨髓间充质干细胞细胞外基质重塑潜能。
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