Microvascular endothelial heterogeneity

The goal of this study was to gain insight into the molecular heterogeneity of capillary endothelial cells derived from different organs by microarray profiling of freshly isolated cells and identify transcription factors that may determine the specific gene expression profile of endothelial cells from different tissues. The study focused on heart endothelial cells and presents a validated signature of 31 genes that are highly enriched in heart endothelial cells. Within this signature 5 transcription factors were identified and the optimal combination of these transcription factors was determined for specification of the heart endothelial fingerprint. From three tissue types (mouse brain, heart and liver), we collected five freshly isolated endothelial cell samples each. For each brain sample we pooled RNA from 6 mice. For each heart sample we pooled RNA from 4 mice. For each liver sample we pooled RNA from 2 mice. The three endothelial subtypes were then compared. For each subtype, specific gene profiles were defined by determining the genes that were highly enriched versus the other two endothelial subtypes.

本研究旨在通过对新鲜分离的毛细血管内皮细胞进行微阵列（microarray）谱分析，解析不同器官来源的毛细血管内皮细胞的分子异质性，并鉴定可调控不同组织内皮细胞特异性基因表达谱的转录因子（transcription factor）。本研究聚焦于心脏内皮细胞，报道了一组经验证的、在心脏内皮细胞中高度富集的31个基因特征标记；该标记中共鉴定出5个转录因子，并确定了这些转录因子的最优组合，以确立心脏内皮细胞的特异性分子指纹。我们从三种组织类型（小鼠脑、心脏和肝脏）中各采集了5份新鲜分离的内皮细胞样本：每份脑样本混合6只小鼠的RNA，每份心脏样本混合4只小鼠的RNA，每份肝脏样本混合2只小鼠的RNA。随后对这三种内皮细胞亚型开展比较分析：通过筛选相较于另外两种内皮细胞亚型显著富集的基因，定义出每种亚型特有的基因表达谱。