Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, 35392 Giessen, Germany.
Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, 35392 Giessen, Germany; Institute for Lung Health (ILH), 35392 Giessen, Germany.
Cell Rep. 2020 Dec 22;33(12):108549. doi: 10.1016/j.celrep.2020.108549.
Tissue regeneration requires coordinated and dynamic remodeling of stem and progenitor cells and the surrounding niche. Although the plasticity of epithelial cells has been well explored in many tissues, the dynamic changes occurring in niche cells remain elusive. Here, we show that, during lung repair after naphthalene injury, a population of PDGFRα cells emerges in the non-cartilaginous conducting airway niche, which is normally populated by airway smooth muscle cells (ASMCs). This cell population, which we term "repair-supportive mesenchymal cells" (RSMCs), is distinct from conventional ASMCs, which have previously been shown to contribute to epithelial repair. Gene expression analysis on sorted lineage-labeled cells shows that RSMCs express low levels of ASMC markers, but high levels of the pro-regenerative marker Fgf10. Organoid co-cultures demonstrate an enhanced ability for RSMCs in supporting club-cell growth. Our study highlights the dynamics of mesenchymal cells in the airway niche and has implications for chronic airway-injury-associated diseases.
组织再生需要干细胞和祖细胞及其周围生态位的协调和动态重塑。尽管上皮细胞的可塑性在许多组织中得到了很好的研究，但生态位细胞中发生的动态变化仍然难以捉摸。在这里，我们表明，在萘损伤后的肺修复过程中，一群 PDGFRα 细胞出现在非软骨性传导气道生态位中，而该生态位通常由气道平滑肌细胞（ASMCs）组成。我们将这群细胞称为“修复支持性间充质细胞”（RSMCs），它们与先前被证明有助于上皮修复的传统 ASMCs 不同。对分选的谱系标记细胞进行基因表达分析表明，RSMCs 表达低水平的 ASMC 标志物，但高水平的促再生标志物 Fgf10。类器官共培养证明 RSMCs 具有更强的支持 club 细胞生长的能力。我们的研究强调了气道生态位中间充质细胞的动态变化，并对慢性气道损伤相关疾病具有重要意义。
