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首页> 外文期刊>Stem cell research >A systems biology approach to identify niche determinants of cellular phenotypes - ScienceDirect
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A systems biology approach to identify niche determinants of cellular phenotypes - ScienceDirect

机译：识别细胞表型利基决定因素的系统生物学方法-ScienceDirect

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Recent reports indicate a dominant role for cellular microenvironment or niche for stably maintaining cellular phenotypic states. Identification of key niche mediated signaling that maintains stem cells in specific phenotypic states remains a challenge, mainly due to the complex and dynamic nature of stem cell-niche interactions. In order to overcome this, we consider that stem cells maintain their phenotypic state by experiencing a constant effect created by the niche by integrating its signals via signaling pathways. Such a constant niche effect should induce sustained activation/inhibition of specific stem cell signaling pathways that controls the gene regulatory program defining the cellular phenotypic state. Based on this view, we propose a computational approach to identify the most likely receptor mediated signaling responsible for transmitting niche signals to the transcriptional regulatory network that maintain cell-specific gene expression patterns, termed as niche determinants. We demonstrate the utility of our method in different stem cell systems by identifying several known and novel niche determinants. Given the key role of niche in several degenerative diseases, identification of niche determinants can aid in developing strategies for potential applications in regenerative medicine.
机译：最近的报道表明细胞微环境或生态位在稳定维持细胞表型状态中起着主导作用。将干细胞保持在特定表型状态的关键利基介导的信号传导的鉴定仍然是一个挑战，主要是由于干细胞-利基相互作用的复杂和动态性质。为了克服这个问题，我们认为干细胞通过经历小生境通过信号传导途径整合其信号而产生的恒定效应，从而维持其表型状态。这种持续的利基效应应诱导特定干细胞信号传导途径的持续活化/抑制，该途径控制定义细胞表型状态的基因调节程序。基于此观点，我们提出了一种计算方法，以识别最有可能的受体介导的信号，该信号负责将小生境信号传递至维持细胞特异性基因表达模式（称为小生境决定因素）的转录调控网络。我们通过确定几个已知和新颖的利基决定因素，证明了我们的方法在不同干细胞系统中的实用性。鉴于生态位在几种退行性疾病中的关键作用，确定生态位决定因素可以帮助制定在再生医学中潜在应用的策略。

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