论文标题

鉴定血细胞发育中控制细胞命运的生物标志物

Identification of Biomarkers Controlling Cell Fate In Blood Cell Development

论文作者

Nazarieh, Maryam, Helms, Volkhard, Hoeppner, Marc P., Franke, Andre

论文摘要

血细胞谱系由多个连续的发育阶段组成,从多能干细胞到末端分化状态。尽管对人类生物学的重要性,但尚未完全理解控制这些差异化过程的监管途径和基因网络。这部分是由于与描述转录因子(TFS)及其目标基因之间相互作用有关的挑战。越来越多的表达数据作为链接分化阶段和基因活动的基础提供了一个可能的前进路径。在这里,我们提出了一种新型的分层方法,以识别全局调节剂沿细胞谱系的分化路径暴露的特征表达峰模式。基于这种简单的模式,我们识别细胞状态特异性标记基因并提取可能驱动其分化的TF。阶段特异性关键玩家基因的平均表达值的集成为每个谱系产生独特的峰值模式,用于识别数据集中的进一步基因的行为相似。结合了在控制细胞命运生物学过程的一组特定阶段调节剂中调节这些基因的TF集。作为概念证明,我们考虑了两个表达数据集,其中涵盖了小鼠血细胞形成中的关键分化事件。

A blood cell lineage consists of several consecutive developmental stages from the pluri- or multipotent stem cell to a state of terminal differentiation. Despite their importance for human biology, the regulatory pathways and gene networks that govern these differentiation processes are not yet fully understood. This is in part due to challenges associated with delineating the interactions between transcription factors (TFs) and their target genes. A possible path forward in this issue is provided by increasingly available expression data as a basis for linking differentiation stages and gene activities. Here, we present a novel hierarchical approach to identify characteristic expression peak patterns that global regulators expose along the differentiation path of cell lineages. Based on such simple patterns, we identify cell state-specific marker genes and extract TFs that likely drive their differentiation. Integration of the mean expression values of stage-specific key player genes yields a distinct peaking pattern for each lineage that is used to identify further genes in the dataset behaving similarly. Incorporating the set of TFs which regulate these genes incurred at a set of stage-specific regulators controlling the biological process of cell fate. As proof of concept, we consider two expression datasets covering key differentiation events in blood cell formation of mice.

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