Integrative genomic and epigenomic profiling reveals cell-type specific signaling networks in activated lung mononuclear phagocytes [RNA-seq]

The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey the lung. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly understood. Here, systematic evaluation of transcriptomes and open chromatin of alveolar macrophages (AMs), interstitial macrophages (IMs) and lung monocytes from two mouse strains enabled inference of common and cell-specific transcriptional regulators. We provide evidence that these factors drive selection of regulatory landscapes that specify distinct phenotypes of AMs and IMs and entrain qualitatively different responses to TLR4 signaling in vivo. These studies reveal a striking divergence in a fundamental innate immune response pathway in AMs and establish a framework for further understanding macrophage diversity in the lung. Low input RNA-seq for alveolar macrophages (AM), interstitial macrophages (IM) and inflammatory monocytes (iMo) isolated from the lung of C57BL/6J mice after intraperitoneal LPS and intranasal LPS administration respectively at 0h, 2h, 6h and 22h.

肺部定居有常驻肺泡巨噬细胞、间质巨噬细胞以及执行肺部监测功能的单核细胞类群。各类细胞在稳态与炎症状态下发挥着截然不同的功能，但塑造其分子身份与功能潜能的核心机制仍未得到充分解析。本研究对两种小鼠品系来源的肺泡巨噬细胞（AMs）、间质巨噬细胞（IMs）与肺部单核细胞的转录组及开放染色质进行了系统性分析，进而推断出共有的及细胞特异性的转录调控因子。我们的研究证实，这些调控因子可驱动调控景观的塑造，进而确定肺泡巨噬细胞与间质巨噬细胞的独特表型，并引发体内针对Toll样受体4（TLR4）信号通路的差异化应答反应。本研究揭示了肺泡巨噬细胞在核心先天免疫应答通路中的显著分化，并为进一步解析肺部巨噬细胞的多样性构建了研究框架。本数据集包含分别经腹腔注射脂多糖（LPS）与鼻内给予脂多糖（LPS）处理后，于0h、2h、6h、22h从C57BL/6J小鼠肺部分离得到的肺泡巨噬细胞（AM）、间质巨噬细胞（IM）与炎性单核细胞（iMo）的低起始量RNA测序（RNA-seq）数据。