Graduate School of Natural and Applied Sciences, Erciyes University, Kayseri 38039, Turkey.
Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri 38039, Turkey.
Int J Mol Sci. 2021 Feb 19;22(4):2064. doi: 10.3390/ijms22042064.
Muse cells are adult stem cells that are present in the stroma of several organs and possess an enduring capacity to cope with endogenous and exogenous genotoxic stress. In cell therapy, the peculiar biological properties of Muse cells render them a possible natural alternative to mesenchymal stromal cells (MSCs) or to in vitro-generated pluripotent stem cells (iPSCs). Indeed, some studies have proved that Muse cells can survive in adverse microenvironments, such as those present in damaged/injured tissues. We performed an evaluation of Muse cells' proteome under basic conditions and followed oxidative stress treatment in order to identify ontologies, pathways, and networks that can be related to their enduring stress capacity. We executed the same analysis on iPSCs and MSCs, as a comparison. The Muse cells are enriched in several ontologies and pathways, such as endosomal vacuolar trafficking related to stress response, ubiquitin and proteasome degradation, and reactive oxygen scavenging. In Muse cells, the protein-protein interacting network has two key nodes with a high connectivity degree and betweenness: NFKB and CRKL. The protein NFKB is an almost-ubiquitous transcription factor related to many biological processes and can also have a role in protecting cells from apoptosis during exposure to a variety of stressors. CRKL is an adaptor protein and constitutes an integral part of the stress-activated protein kinase (SAPK) pathway. The identified pathways and networks are all involved in the quality control of cell components and may explain the stress resistance of Muse cells.
Muse 细胞是存在于多种器官基质中的成体干细胞，具有应对内源性和外源性遗传毒性应激的持久能力。在细胞治疗中，Muse 细胞的独特生物学特性使它们成为间充质基质细胞 (MSCs) 或体外生成的多能干细胞 (iPSCs) 的一种可能的天然替代物。事实上，一些研究已经证明 Muse 细胞可以在不利的微环境中存活，例如存在于受损/受伤组织中的微环境。我们在基本条件下对 Muse 细胞的蛋白质组进行了评估，并进行了氧化应激处理，以鉴定与其持久应激能力相关的本体、途径和网络。我们对 iPSCs 和 MSCs 进行了相同的分析，作为比较。Muse 细胞富含多种本体和途径，例如与应激反应相关的内体小泡运输、泛素和蛋白酶体降解以及活性氧清除。在 Muse 细胞中，蛋白质-蛋白质相互作用网络有两个具有高连接度和中间度的关键节点：NFKB 和 CRKL。蛋白 NFKB 是一种几乎普遍存在的转录因子，与许多生物过程有关，在暴露于各种应激源时，也可以在保护细胞免受凋亡中发挥作用。CRKL 是一种衔接蛋白，是应激激活蛋白激酶 (SAPK) 途径的组成部分。所鉴定的途径和网络都参与细胞成分的质量控制，并可能解释 Muse 细胞的应激抗性。
