BACKGROUND Classic dendritic cells (cDCs) play a central role in the immune system by processing and presenting antigens to activate T cells, and consist of two major subsets: CD141+ cDC (cDC1) and CD1c+ cDC (cDC2). A population of migratory precursor cells, the pre-cDCs, is the immediate precursors to both cDC subsets. Previous studies showed that there were two pre-committed pre-cDC subpopulations. However, the key molecular drivers of pre-commitment in human pre-cDCs were not investigated. RESULTS To identify the key molecular drivers for pre-commitment in human pre-cDCs, we performed single cell RNA sequencing (RNA-Seq) of two cDC subsets and pre-cDCs, and bulk RNA-Seq of pre-cDCs and cDCs from human peripheral blood. We found that pre-DC subpopulations cannot be separated by either variable genes within pre-cDCs or differentially expressed genes between cDC1 and cDC2. In contrast, they were separated by 16 transcription factors that are themselves differentially expressed or have regulated targets enriched in the differentially expressed genes between bulk cDC1 and cDC2, with one subpopulation close to cDC1 and the other close to cDC2. More importantly, these two pre-cDC sub-populations are correlated with ratio of IRF8 to IRF4 expression level more than their individual expression level. We also verified these findings using three recently published datasets. CONCLUSIONS In this study, we demonstrate that single cell transcriptome profiling can reveal pre-cDCs differentiation map, and our results suggest the concept that combinatorial dose of transcription factors determines cell differentiation fate.

中文翻译：

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单细胞 RNA-Seq 揭示了由转录因子组合剂量决定的前 cDCs 命运。

背景 经典树突状细胞 (cDC) 通过加工和呈递抗原以激活 T 细胞在免疫系统中发挥核心作用，并由两个主要亚群组成：CD141+ cDC (cDC1) 和 CD1c+ cDC (cDC2)。迁移前体细胞群，即前 cDC，是两个 cDC 亚群的直接前体。先前的研究表明，有两个预先承诺的前 cDC 亚群。然而，尚未研究人类前 cDC 中预先承诺的关键分子驱动因素。结果 为了确定人类前 cDC 中预先承诺的关键分子驱动因素，我们对两个 cDC 亚群和前 cDC 进行了单细胞 RNA 测序 (RNA-Seq)，并对来自人类的前 cDC 和 cDC 进行了批量 RNA 测序。外周血。我们发现 pre-DC 亚群不能被 pre-cDC 内的可变基因或 cDC1 和 cDC2 之间的差异表达基因分开。相比之下，它们被 16 个转录因子分开，这些转录因子本身差异表达或调节靶点富含大量 cDC1 和 cDC2 之间的差异表达基因，其中一个亚群接近 cDC1，另一个亚群接近 cDC2。更重要的是，这两个前 cDC 亚群与 IRF8 与 IRF4 表达水平的比率的相关性大于它们各自的表达水平。我们还使用三个最近发布的数据集验证了这些发现。结论 在这项研究中，我们证明单细胞转录组分析可以揭示前 cDCs 分化图，