El Agha Elie, Bellusci Saverio
Department of Internal Medicine II, Universities of Giessen and Marburg Lung Center (UGMLC), Klinikstraße 36, 35392 Giessen, Hessen, Germany ; Member of the German Center for Lung Research (DZL), 35392 Giessen, Hessen, Germany.
Department of Internal Medicine II, Universities of Giessen and Marburg Lung Center (UGMLC), Klinikstraße 36, 35392 Giessen, Hessen, Germany ; Member of the German Center for Lung Research (DZL), 35392 Giessen, Hessen, Germany ; Developmental Biology and Regenerative Program of the Saban Research Institute at Childrens Hospital Los Angeles and University of Southern California, Los Angeles, CA 90027, USA.
Scientifica (Cairo). 2014;2014:538379. doi: 10.1155/2014/538379. Epub 2014 Sep 11.
Basic research on embryonic lung development offers unique opportunities to make important discoveries that will impact human health. Developmental biologists interested in the molecular control of branching morphogenesis have intensively studied the developing lung, with its complex and seemingly stereotyped ramified structure. However, it is also an organ that is linked to a vast array of clinical problems in humans such as bronchopulmonary dysplasia in premature babies and emphysema, chronic obstructive pulmonary disease, fibrosis, and cancer in adults. Epithelial stem/progenitor cells reside in niches where they interact with specific extracellular matrices as well as with mesenchymal cells; the latter are still poorly characterized. Interactions of epithelial stem/progenitor cells with their microenvironments are usually instructive, controlling quiescence versus activation, proliferation, differentiation, and migration. During the past 18 years, Fgf10 has emerged not only as a marker for the distal lung mesenchyme during early lung development, but also as a key player in branching morphogenesis and a critical component of the niche for epithelial stem cells. In this paper, we will present the current knowledge regarding the lineage tree in the lung, with special emphasis on cell-lineage decisions in the lung mesenchyme and the role of Fgf10 in this context.
胚胎肺发育的基础研究为做出将影响人类健康的重要发现提供了独特的机会。对分支形态发生的分子控制感兴趣的发育生物学家对发育中的肺进行了深入研究，其具有复杂且看似定型的分支结构。然而，它也是一个与人类大量临床问题相关的器官，如早产儿的支气管肺发育不良以及成年人的肺气肿、慢性阻塞性肺疾病、纤维化和癌症。上皮干细胞/祖细胞存在于特定微环境中，在那里它们与特定的细胞外基质以及间充质细胞相互作用；后者的特征仍不清楚。上皮干细胞/祖细胞与其微环境的相互作用通常具有指导作用，控制着静止与激活、增殖、分化和迁移。在过去的18年里，Fgf10不仅已成为肺早期发育过程中远端肺间充质的标志物，而且还成为分支形态发生的关键参与者以及上皮干细胞微环境的重要组成部分。在本文中，我们将介绍有关肺中谱系树的当前知识，特别强调肺间充质中的细胞谱系决定以及Fgf10在此背景下的作用。
