Gene regulatory networks (GRNs) provide a powerful framework for studying cellular differentiation. However, it is less clear how GRNs encode cellular responses to everyday microenvironmental cues. Macrophages can be polarized and potentially repolarized based on environmental signaling. In order to identify the GRNs that drive macrophage polarization and the heterogeneous single-cell subpopulations that are present in the process, we used a high-resolution time course of bulk and single-cell RNA-seq and ATAC-seq assays of HL-60-derived macrophages polarized towards M1 or M2 over 24 hours. We identified transient M1 and M2 markers, including the main transcription factors that underlie polarization, and subpopulations of naive, transitional, and terminally polarized macrophages. We built bulk and single-cell polarization GRNs to compare the recovered interactions and found that each technology recovered only a subset of known interactions. Our data provide a resource to study the GRN of cellular maturation in response to microenvironmental stimuli in a variety of contexts in homeostasis and disease.

中文翻译：

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通过对散装和单细胞数据的比较分析，发现巨噬细胞极化背后的基因调控网络

基因调控网络（GRN）为研究细胞分化提供了强大的框架。然而，还不清楚GRNs如何编码对日常微环境线索的细胞反应。巨噬细胞可根据环境信号极化，并可能重新极化。为了识别驱动巨噬细胞极化的GRN和该过程中存在的异质单细胞亚群，我们使用了HL-60的批量和单细胞RNA-seq和ATAC-seq分析的高分辨率时程衍生的巨噬细胞在24小时内朝M1或M2极化。我们鉴定了瞬时的M1和M2标记，包括极化基础上的主要转录因子以及天真，过渡和末端极化巨噬细胞的亚群。我们构建了体细胞和单细胞极化GRN，以比较回收的相互作用，发现每种技术仅回收了已知相互作用的一部分。我们的数据为研究在稳态和疾病的多种情况下对微环境刺激的细胞成熟的GRN提供了资源。