Gene expression programs of mouse endothelial cells in kidney development and disease.
Gene expression programs of mouse endothelial cells in kidney development and disease.
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DOI：
10.1371/journal.pone.0012034
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发表时间：
2010-08-10
期刊：
影响因子：
3.7
通讯作者：
Potter SS
中科院分区：
文献类型：
--
作者：
Brunskill EW;Potter SS
内皮细胞在形态和功能上具有显著的异质性，它们在多器官系统的形成中起着至关重要的作用。此外，内皮细胞功能障碍可以促进疾病进程，包括糖尿病肾病，这是终末期肾脏疾病的主要原因。在本报告中，我们定义了多种类型肾内皮细胞的综合基因表达程序，并分析了区分它们的差异。采用细胞分离和荧光活化细胞分选的方法纯化了Tie2-GFP小鼠的内皮细胞。然后使用微阵列提供基因表达水平的全局、定量和敏感测量。我们检查了胚胎和成年肾小球、皮质和髓质室的肾内皮细胞，以及db/db突变小鼠的肾小球内皮细胞，db/db突变小鼠代表了人类糖尿病肾病的模型。结果确定了多种内皮细胞类型表达的生长因子、受体和转录因子。对生物过程和分子途径进行了详细的描述。定义了细胞类型特异性基因表达模式，发现了新的分子标记，并提供了更好的理解区隔差异。此外，对共激活基因启动子中富集的、进化上保守的转录因子结合位点的分析开始定义肾内皮细胞形成的遗传调控网络。最后，定义了与糖尿病肾病相关的基因表达差异，提供了激活的致病和保护途径的全局视图。这些研究为进一步研究内皮细胞在肾脏发育、成人室和疾病中的功能提供了丰富的资源。
Endothelial cells are remarkably heterogeneous in both morphology and function, and they play critical roles in the formation of multiple organ systems. In addition endothelial cell dysfunction can contribute to disease processes, including diabetic nephropathy, which is a leading cause of end stage renal disease. In this report we define the comprehensive gene expression programs of multiple types of kidney endothelial cells, and analyze the differences that distinguish them. Endothelial cells were purified from Tie2-GFP mice by cell dissociation and fluorescent activated cell sorting. Microarrays were then used to provide a global, quantitative and sensitive measure of gene expression levels. We examined renal endothelial cells from the embryo and from the adult glomerulus, cortex and medulla compartments, as well as the glomerular endothelial cells of the db/db mutant mouse, which represents a model for human diabetic nephropathy. The results identified the growth factors, receptors and transcription factors expressed by these multiple endothelial cell types. Biological processes and molecular pathways were characterized in exquisite detail. Cell type specific gene expression patterns were defined, finding novel molecular markers and providing a better understanding of compartmental distinctions. Further, analysis of enriched, evolutionarily conserved transcription factor binding sites in the promoters of co-activated genes begins to define the genetic regulatory network of renal endothelial cell formation. Finally, the gene expression differences associated with diabetic nephropathy were defined, providing a global view of both the pathogenic and protective pathways activated. These studies provide a rich resource to facilitate further investigations of endothelial cell functions in kidney development, adult compartments, and disease.
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