Characterizing transcriptional heterogeneity through pathway and gene set overdispersion analysis (PAGODA)

The extent of transcriptional diversity in mouse NPCs is likely to be influenced by a variety of unexamined factors that include programmed cell death, genomic mosaicism as well as a variety of "environmental" influences such as changes in exposure to signaling lipids. We therefore used scRNA-seq to assess a cohort of cortical NPCs from an embryonic mouse. We demonstrate that PAGODA (Pathway And Geneset OverDispersion Analysis) effectively recovers the known neuroanatomical and functional organization of NPCs, identifying multiple aspects of transcriptional heterogeneity within the developing mouse cortex that are difficult to discern by the existing heterogeneity analysis approaches. Examination of mouse NPC transcriptional heterogeneity via single cell RNA-seq小鼠神经前体细胞（Neural Progenitor Cells, NPC）的转录多样性程度，大概率受到多种未被探究的因素影响，这些因素涵盖细胞程序性死亡、基因组嵌合现象，以及诸如信号脂质暴露水平变化等多种“环境性”影响因素。为此，我们采用单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）技术，对一批胚胎小鼠的皮层神经前体细胞队列进行了评估。研究证实，PAGODA（通路与基因集过度分散分析，Pathway And Geneset OverDispersion Analysis）可有效还原已知的神经前体细胞神经解剖学与功能组织特征，并识别出发育中小鼠皮层内多种难以通过现有异质性分析方法辨析的转录异质性维度。 基于单细胞RNA测序的小鼠神经前体细胞转录异质性研究