Discordant roles for FGF ligands in lung branching morphogenesis between human and mouse.
Discordant roles for FGF ligands in lung branching morphogenesis between human and mouse.
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DOI：
10.1002/path.5188
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Al Alam D
中科院分区：
文献类型：
--
作者：
Danopoulos S;Thornton ME;Grubbs BH;Frey MR;Warburton D;Bellusci S;Al Alam D
成纤维细胞生长因子（FGF）信号转导在肺器官发生中起重要作用。近几十年来，肺发育中的FGF信号转导已在动物模型中得到广泛研究。然而，很少有人知道FGF配体在人胎肺发育过程中的表达，定位和功能作用。因此，我们旨在确定几种FGF配体和受体在人肺发育中的表达和功能。利用原位杂交（ISH）和RNA测序，我们评估了他们的表达和分布在自然人胎肺。在气液界面培养中用重组FGF 7、FGF 9或FGF 10处理人胎肺外植体。对外植体进行了大体分析，以观察分支模式以及细胞和分子水平的差异。ISH表明，FGF 7在上皮和间充质中表达; FGF 9主要位于远端上皮中，而FGF 10在整个实质中弥漫表达，在平滑肌细胞（SMC）中有一些表达。FGFR 2在近端和远端上皮细胞以及SMCs中均高表达。FGFR 3主要在上皮细胞中表达，在间充质中表达较低，而FGFR 4在整个间充质和远端上皮中高度表达。使用重组FGF，我们证明了FGF 7和FGF 9对人胎肺的作用与对小鼠的作用相似;然而，FGF 10导致人外植体扩张并形成囊肿，而不是诱导小鼠中观察到的上皮分支。与分支减少相结合，用重组FGF 7、FGF 9和FGF 10处理也导致双阳性SOX 2/SOX 9祖细胞减少，所述祖细胞仅存在于早期人胎儿肺的远端上皮尖端中。虽然FGF配体定位在发育中的小鼠和人肺之间可能有些可比性，但它们的功能作用可能有很大不同。
Fibroblast Growth Factor (FGF) signaling plays an important role in lung organogenesis. Over recent decades, FGF signaling in lung development has been extensively studied in animal models. However, little is known about the expression, localization and functional roles of FGF ligands during human fetal lung development. Therefore, we aimed to determine the expression and function of several FGF ligands and receptors in human lung development. Using in situ hybridization (ISH) and RNA-sequencing, we assessed their expression and distribution in native human fetal lung. Human fetal lung explants were treated with recombinant FGF7, FGF9 or FGF10 in air-liquid interface culture. Explants were analyzed grossly, to observe differences in branching pattern, as well as at the cellular and molecular level. ISH demonstrated that FGF7 is expressed in both the epithelium and mesenchyme; FGF9 is mainly localized in the distal epithelium, whereas FGF10 demonstrated diffuse expression throughout the parenchyma with some expression in the smooth muscle cells (SMCs). FGFR2 expression was high in both proximal and distal epithelial cells as well as the SMCs. FGFR3 was expressed mostly in the epithelial cells, with lower expression in the mesenchyme, while FGFR4 was highly expressed throughout the mesenchyme and in the distal epithelium. Using recombinant FGFs, we demonstrated that FGF7 and FGF9 had similar effects on human fetal lung as on mouse; however, FGF10 caused the human explants to expand and form cysts as opposed to inducing epithelial branching as seen in the mouse. In conjunction with decreased branching, treatment with recombinant FGF7, FGF9 and FGF10 also resulted in decreased double-positive SOX2/SOX9 progenitor cells, which are exclusively present in the distal epithelial tips in early human fetal lung. Although FGF ligand localization may be somewhat comparable between developing mouse and human lungs, their functional roles may differ substantially.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
DOI：
10.1152/ajplung.00033.2004
发表时间：
2004-12-01
影响因子：
4.9
作者：
Hyatt, BA;Shangguan, XF;Shannon, JM
通讯作者：
Shannon, JM
影响因子：
2.5
作者：
El Agha, Elie;Kheirollahi, Vahid;Bellusci, Saverio
通讯作者：
Bellusci, Saverio
DOI：
10.1164/rccm.200907-1063oc
发表时间：
2010-01-01
影响因子：
24.7
作者：
Kho, Alvin T.;Bhattacharya, Soumyaroop;Mariani, Thomas J.
通讯作者：
Mariani, Thomas J.