The lung is an architecturally complex organ comprising a heterogeneous mixture of various epithelial and mesenchymal lineages. We use single-cell RNA sequencing and signaling lineage reporters to generate a spatial and transcriptional map of the lung mesenchyme. We find that each mesenchymal lineage has a distinct spatial address and transcriptional profile leading to unique niche regulatory functions. The mesenchymal alveolar niche cell is Wnt responsive, expresses Pdgfrα, and is critical for alveolar epithelial cell growth and self-renewal. In contrast, the Axin2+ myofibrogenic progenitor cell preferentially generates pathologically deleterious myofibroblasts after injury. Analysis of the secretome and receptome of the alveolar niche reveals functional pathways that mediate growth and self-renewal of alveolar type 2 progenitor cells, including IL-6/Stat3, Bmp, and Fgf signaling. These studies define the cellular and molecular framework of lung mesenchymal niches and reveal the functional importance of developmental pathways in promoting self-renewal versus a pathological response to tissue injury.

中文翻译：

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不同的间充质谱系和壁Pro促进了肺的上皮自我更新和肌纤维化。

肺是结构复杂的器官，包括各种上皮和间充质谱系的异质混合物。我们使用单细胞RNA测序和信号传承记者生成肺间充质的空间和转录图。我们发现每个间充质谱系有一个独特的空间地址和转录谱导致独特的利基调节功能。间充质肺泡小生境细胞具有Wnt反应性，表达Pdgfrα，对肺泡上皮细胞的生长和自我更新至关重要。相反，Axin2 +肌成纤维祖细胞在损伤后优先产生对病理有害的成肌纤维细胞。对肺泡小生境的分泌组和受体组的分析揭示了介导2型肺泡祖细胞生长和自我更新的功能性途径，包括IL-6 / Stat3，Bmp和Fgf信号。这些研究定义了肺间充质生境的细胞和分子框架，并揭示了发育途径在促进自我更新与对组织损伤的病理反应中的功能重要性。