Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment
Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment
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DOI：
10.1182/blood-2006-10-053280
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发表时间：
2007-06-01
期刊：
影响因子：
20.3
通讯作者：
Maurer, Dieter
中科院分区：
文献类型：
--
作者：
Amatschek, Stefan;Kriehuber, Ernst;Maurer, Dieter
人类血液（BEC）和淋巴管内皮细胞（LEC）标记蛋白的发现使研究人员能够分离这些细胞。到目前为止，解开它们的转录和功能程序的努力只利用了培养的细胞。因此，它是未知的，在何种程度上先前确定的LEC和BEC特异性程序是代表在体内的情况。在这里，我们定义了人类BEC和LEC特异性体内转录组的比较基因组表达谱的新鲜分离的皮肤EC子集和非EC皮肤细胞（成纤维细胞，肥大细胞，树突状细胞，上皮细胞）。有趣的是，大多数新发现的EC亚群识别基因的表达严格依赖于体内组织环境，如新鲜分离和培养的EC亚群的比较分析所揭示的。所确定的环境依赖性，EC亚群限制性基因表达调节谱系保真度，流体交换和MHC II类依赖性抗原呈递。作为一个例子，在体内功能的BEC限制，我们表明，非活化的BEC在原位，但不是在体外，组装和展示MHC II类蛋白复合物装载自肽。因此，我们的数据证明了使用精确定义的天然EC用于体内相关细胞功能的全局识别的关键重要性。
The discovery of marker proteins of human blood (BECs) and lymphatic endothelial cells (LECs) has allowed researchers to isolate these cells. So far, efforts to unravel their transcriptional and functional programs made use of cultured cells only. Hence, it is unknown to which extent previously identified LEC- and BEC-specific programs are representative of the in vivo situation. Here, we define the human BEC- and LEC-specific in vivo transcriptomes by comparative genomewide expression profiling of freshly isolated cutaneous EC subsets and of non-EC skin cells (fibroblasts, mast cells, dendritic cells, epithelial cells). Interestingly, the expression of most of the newly identified EC subset-discriminating genes depends strictly on the in vivo tissue environment as revealed by comparative analyses of freshly isolated and cultured EC subsets. The identified environment-dependent, EC subset-restricted gene expression regulates lineage fidelity, fluid exchange, and MHC class II-dependent antigen presentation. As an example for a BEC-restricted in vivo function, we show that non-activated BECs in situ, but not in vitro, assemble and display MHC class II protein complexes loaded with self-peptides. Thus, our data demonstrate the key importance of using precisely defined native ECs for the global identification of in vivo relevant cell functions.