Ravichandran Srikanth, Okawa Satoshi, Martínez Arbas Susana, Del Sol Antonio
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg.
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg.
Stem Cell Res. 2016 Sep;17(2):406-412. doi: 10.1016/j.scr.2016.09.006. Epub 2016 Sep 15.
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.
最近的报告表明，细胞微环境或生态位在稳定维持细胞表型状态方面起主导作用。识别在特定表型状态下维持干细胞的关键生态位介导信号仍然是一项挑战，主要是由于干细胞与生态位相互作用的复杂性和动态性。为了克服这一问题，我们认为干细胞通过整合其信号经由信号通路来感受生态位产生的恒定效应，从而维持其表型状态。这种恒定的生态位效应应诱导特定干细胞信号通路的持续激活/抑制，该信号通路控制定义细胞表型状态的基因调控程序。基于这一观点，我们提出一种计算方法，以识别最有可能的受体介导信号，该信号负责将生态位信号传递至维持细胞特异性基因表达模式的转录调控网络，我们将其称为生态位决定因素。我们通过识别几个已知的和新的生态位决定因素，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，识别生态位决定因素有助于制定在再生医学中潜在应用的策略。
