背景:在几乎所有实体组织中都发现了两个主要的巨噬细胞亚类:胚胎来源的常驻组织巨噬细胞和骨髓来源的浸润巨噬细胞。这些巨噬细胞亚型表现出转录和功能分歧,而影响肾巨噬细胞和相关信号通路进化的程序仍然知之甚少。为了澄清这些过程,我们基于人肾组织驻留和浸润巨噬细胞的单细胞转录谱进行数据分析,老鼠和老鼠
结果:在这项研究中,我们(i)表征了物种之间的转录差异,(ii)说明了每种亚型细胞之间表达的变异性,(iii)比较了基因调控网络和(iv)人和小鼠中的配体-受体对。使用单细胞转录组学,我们绘制了稳态过程中的启动子结构。
结论:转录差异基因,例如在这三个物种的常驻和浸润巨噬细胞中表达的差异TF编码基因,不同的细胞,包括不同的启动子结构。浸润巨噬细胞中的基因调控网络比常驻巨噬细胞显示出相对更好的物种范围一致性。物种间浸润巨噬细胞中保守的转录基因调控网络独特地富集在与激酶相关的通路中,与物种之间的大部分保守的调节子相关的TF在激酶相关途径中独特地富集。
BACKGROUND: Two main subclasses of macrophages are found in almost all solid tissues: embryo-derived resident tissue macrophages and bone marrow-derived infiltrated macrophages. These macrophage subtypes show transcriptional and functional divergence, and the programs that have shaped the evolution of renal macrophages and related signaling pathways remain poorly understood. To clarify these processes, we performed data analysis based on single-cell transcriptional profiling of renal tissue-resident and infiltrated macrophages in human, mouse and rat.
RESULTS: In this study, we (i) characterized the transcriptional divergence among species and (ii) illustrated variability in expression among cells of each subtype and (iii) compared the gene regulation network and (iv) ligand-receptor pairs in human and mouse. Using single-cell transcriptomics, we mapped the promoter architecture during homeostasis.
CONCLUSIONS: Transcriptionally divergent genes, such as the differentially TF-encoding genes expressed in resident and infiltrated macrophages across the three species, vary among cells and include distinct promoter structures. The gene regulatory network in infiltrated macrophages shows comparatively better species-wide consistency than resident macrophages. The conserved transcriptional gene regulatory network in infiltrated macrophages among species is uniquely enriched in pathways related to kinases, and TFs associated with largely conserved regulons among species are uniquely enriched in kinase-related pathways.