Fgf10-positive cells represent a progenitor cell population during lung development and postnatally
Fgf10-positive cells represent a progenitor cell population during lung development and postnatally
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DOI：
10.1242/dev.099747
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发表时间：
2014-01-15
期刊：
影响因子：
4.6
通讯作者：
Bellusci, Saverio
中科院分区：
文献类型：
--
作者：
El Agha, Elie;Herold, Susanne;Bellusci, Saverio
肺间质由广泛的异质细胞群组成，在出生后的发育和体内平衡中起着至关重要的作用。这些细胞属于肌源性、脂肪源性、软骨源性、神经元和其他谱系。然而，这些血统没有明确的等级制度。我们之前已经生成了一种新的Fgf10（iCre）敲入小鼠系，可以在发育和出生后对Fgf10阳性细胞进行谱系追踪。利用这些小鼠，我们在此证明了在胚胎肺发育过程中存在两波Fgf10表达：第一波，包括早期假腺期居住在间皮下间质中的Fgf10阳性细胞（及其后代）；第二波，包括假腺晚期fgf10阳性细胞（及其后代）。我们的谱系追踪数据显示，第一波有助于在发育后期形成支气管旁和血管平滑肌细胞以及脂肪成纤维细胞，而第二波不会产生平滑肌细胞，但会产生脂肪成纤维细胞以及需要进一步深入分析的Nkx2.1(-) E-Cad(-) Epcam(+) Pro-Spc（+）谱系。在肺泡形成过程中，fgf10阳性细胞产生脂肪成纤维细胞而不是肺泡肌成纤维细胞，在成年期，表达fgf10的细胞亚群代表了一个常驻间充质间质干细胞（MSCs）库(Cd45(-) Cd31（-) Sca-1(+)）。综上所述，我们首次表明表达fgf10的细胞代表胚胎和出生后肺的间充质祖细胞库。我们的研究结果表明，fgf10阳性细胞可能有助于开发基于干细胞的治疗间质性肺疾病的疗法。
The lung mesenchyme consists of a widely heterogeneous population of cells that play crucial roles during development and homeostasis after birth. These cells belong to myogenic, adipogenic, chondrogenic, neuronal and other lineages. Yet, no clear hierarchy for these lineages has been established. We have previously generated a novel Fgf10(iCre) knock-in mouse line that allows lineage tracing of Fgf10-positive cells during development and postnatally. Using these mice, we hereby demonstrate the presence of two waves of Fgf10 expression during embryonic lung development: the first wave, comprising Fgf10-positive cells residing in the submesothelial mesenchyme at early pseudoglandular stage (as well as their descendants); and the second wave, comprising Fgf10-positive cells from late pseudoglandular stage (as well as their descendants). Our lineage-tracing data reveal that the first wave contributes to the formation of parabronchial and vascular smooth muscle cells as well as lipofibroblasts at later developmental stages, whereas the second wave does not give rise to smooth muscle cells but to lipofibroblasts as well as an Nkx2.1(-) E-Cad(-) Epcam(+) Pro-Spc(+) lineage that requires further in-depth analysis. During alveologenesis, Fgf10-positive cells give rise to lipofibroblasts rather than alveolar myofibroblasts, and during adult life, a subpopulation of Fgf10-expressing cells represents a pool of resident mesenchymal stromal (stem) cells (MSCs) (Cd45(-) Cd31(-) Sca-1(+)). Taken together, we show for the first time that Fgf10-expressing cells represent a pool of mesenchymal progenitors in the embryonic and postnatal lung. Our findings suggest that Fgf10-positive cells could be useful for developing stem cell-based therapies for treating interstitial lung diseases.