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计算比较分析确定了间充质基质/干细胞潜在的干性相关标志物。

Computational comparative analysis identifies potential stemness-related markers for mesenchymal stromal/stem cells.

作者信息

Ghabriel Myret, El Hosseiny Ahmed, Moustafa Ahmed, Amleh Asma

机构信息

Biotechnology Graduate Program, American University in Cairo, New Cairo, Egypt.

Department of Biology, American University in Cairo, New Cairo, Egypt.

出版信息

Front Cell Dev Biol. 2023 Mar 1;11:1065050. doi: 10.3389/fcell.2023.1065050. eCollection 2023.

Abstract

Mesenchymal stromal/stem cells (MSCs) are multipotent cells that reside in multiple tissues are capable of self-renewal and differentiation into various cell types. These properties make them promising candidates for regenerative therapies. MSC identification is critical in yielding pure populations for successful therapeutic applications; however, the criteria for MSC identification proposed by the International Society for Cellular Therapy (ISCT) are inconsistent across different tissue sources. This study aimed to identify potential markers to be used together with the ISCT criteria to provide a more accurate means of MSC identification. Thus, we carried out a computational comparative analysis of the gene expression in human and mouse MSCs derived from multiple tissues to identify the differentially expressed genes that are shared between the two species. We show that six members of the proteasome degradation system are similarly expressed across MSCs derived from bone marrow, adipose tissue, amnion, and umbilical cord. Additionally, with the help of predictive models, we found that the expression profile of these genes correctly validated the identity of the MSCs across all the tissue sources tested. Moreover, using genetic interaction networks, we showed a possible link between these genes and antioxidant enzymes in the MSC antioxidant defense system, thereby pointing to their potential role in prolonging the life span of MSCs. According to our findings, members of the proteasome degradation system may serve as stemness-related markers.

摘要

间充质基质/干细胞(MSCs)是多能细胞,存在于多种组织中,能够自我更新并分化为各种细胞类型。这些特性使其成为再生疗法的有前景的候选者。MSC的鉴定对于获得用于成功治疗应用的纯细胞群体至关重要;然而,国际细胞治疗协会(ISCT)提出的MSC鉴定标准在不同组织来源中并不一致。本研究旨在鉴定与ISCT标准一起使用的潜在标志物,以提供一种更准确的MSC鉴定方法。因此,我们对来自多种组织的人和小鼠MSCs中的基因表达进行了计算比较分析,以鉴定这两个物种之间共有的差异表达基因。我们发现蛋白酶体降解系统的六个成员在源自骨髓、脂肪组织、羊膜和脐带的MSCs中表达相似。此外,借助预测模型,我们发现这些基因的表达谱正确验证了所有测试组织来源中MSCs的身份。此外,利用基因相互作用网络,我们展示了这些基因与MSC抗氧化防御系统中的抗氧化酶之间的可能联系,从而指出它们在延长MSCs寿命方面的潜在作用。根据我们的研究结果,蛋白酶体降解系统的成员可能作为干性相关标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1583/10014615/114b44043c93/fcell-11-1065050-g001.jpg

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