Distinct Mesenchymal Lineages and Niches Promote Epithelial Self-Renewal and Myofibrogenesis in the Lung.
Distinct Mesenchymal Lineages and Niches Promote Epithelial Self-Renewal and Myofibrogenesis in the Lung.
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DOI：
10.1016/j.cell.2017.07.034
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发表时间：
2017-09-07
期刊：
影响因子：
64.5
通讯作者：
Morrisey EE
中科院分区：
文献类型：
--
作者：
Zepp JA;Zacharias WJ;Frank DB;Cavanaugh CA;Zhou S;Morley MP;Morrisey EE
肺是一个结构复杂的器官，由各种上皮和间充质谱系的异质混合物组成。我们已经使用单细胞RNA测序和信号传导谱系报告生成肺间充质的空间和转录图谱。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，导致独特的生态位调控功能。间充质肺泡小生境细胞是Wnt反应性的，表达Pdgfrα，并且对肺泡上皮细胞生长和自我更新至关重要。相反，Axin 2+肌纤维原祖细胞在损伤后优先产生病理有害的肌成纤维细胞。对肺泡小生境的分泌组和受体组的分析揭示了介导肺泡2型祖细胞生长和自我更新的功能途径，包括IL-6/Stat 3、Bmp和Fgf信号传导。这些研究定义了肺间充质生态位的细胞和分子框架，并揭示了促进自我更新与组织损伤病理反应的发育途径的功能重要性。
The lung is an architecturally complex organ comprised of a heterogeneous mixture of various epithelial and mesenchymal lineages. We have used 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 promoting self-renewal versus pathological response to tissue injury.
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影响因子：
82.9
作者：
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影响因子：
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DOI：
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发表时间：
2015-07-01
影响因子：
6.4
作者：
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通讯作者：
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DOI：
10.1165/rcmb.2013-0310oc
发表时间：
2015-02-01
影响因子：
6.4
作者：
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