Ex vivo analysis of the contribution of FGF10+ cells to airway smooth muscle cell formation during early lung development
Ex vivo analysis of the contribution of FGF10+ cells to airway smooth muscle cell formation during early lung development
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DOI：
10.1002/dvdy.24504
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发表时间：
2017-07-01
影响因子：
2.5
通讯作者：
Bellusci, Saverio
中科院分区：
文献类型：
--
作者：
El Agha, Elie;Kheirollahi, Vahid;Bellusci, Saverio
背景：气道平滑肌细胞（ASMCs）在胚胎肺发育过程中已被广泛研究。这些细胞已被证明在分支形态发生过程中控制上皮分叉。成纤维细胞生长因子10阳性（FGF 10（+））细胞，最初存在于间皮下间充质中，有助于远端肺中ASMC的形成。本文报道的工作旨在利用气-液界面（ALI）培养系统的谱系示踪技术，真实的实时监测FGF 10（+）祖细胞和分化的ASMCs对生长因子处理的反应。结果：FGF配体在体外对迭代肺分支产生不同的影响。此外，延时成像和终点分析显示，FGF 9处理导致FGF 10（+）谱系扩增并抑制其向ASMC分化。Sonic hedgehog（SHH）治疗减少了该谱系的扩增，并导致肺分支减少。最后，近端区域中的分化的ASMC在FGF 9处理后不能扩增。结论：我们的数据表明，在真实的时间，FGF 9是一个重要的调节剂的扩增，迁移，并随后分化的ASMC祖细胞在早期肺发育。所获得的结果与先前关于ASMC形成的发现一致，并突出了生长因子信号网络在发育中的小鼠肺中控制间充质细胞命运决定的复杂性。发展动力学246：531-538，2017年。(c)2017年Wiley Periodicals，Inc.
Background: Airway smooth muscle cells (ASMCs) have been widely studied during embryonic lung development. These cells have been shown to control epithelial bifurcation during branching morphogenesis. Fibroblast growth factor 10-positive (FGF10(+)) cells, originally residing in the submesothelial mesenchyme, contribute to ASMC formation in the distal lung. The reported work aims at monitoring the response of FGF10(+) progenitors and differentiated ASMCs to growth factor treatment in real time using lineage tracing in the background of an air-liquid interface (ALI) culture system. Results: FGF ligands impose divergent effects on iterative lung branching in vitro. Moreover, time-lapse imaging and endpoint analysis show that FGF9 treatment leads to amplification of the FGF10(+) lineage and represses its differentiation to ASMCs. Sonic hedgehog (SHH) treatment reduces the amplification of this lineage and leads to decreased lung branching. Finally, differentiated ASMCs in proximal regions fail to expand upon FGF9 treatment. Conclusions: Our data demonstrate, in real time, that FGF9 is an important regulator of amplification, migration, and subsequent differentiation of ASMC progenitors during early lung development. The attained results agree with previous findings regarding ASMC formation and highlight the complexity of growth factor signaling networks in controlling mesenchymal cell-fate decisions in the developing mouse lung. Developmental Dynamics 246:531-538, 2017. (c) 2017 Wiley Periodicals, Inc.