Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, NY 10065, USA.
Dev Cell. 2013 Jul 29;26(2):204-19. doi: 10.1016/j.devcel.2013.06.017. Epub 2013 Jul 18.
Microvascular endothelial cells (ECs) within different tissues are endowed with distinct but as yet unrecognized structural, phenotypic, and functional attributes. We devised EC purification, cultivation, profiling, and transplantation models that establish tissue-specific molecular libraries of ECs devoid of lymphatic ECs or parenchymal cells. These libraries identify attributes that confer ECs with their organotypic features. We show that clusters of transcription factors, angiocrine growth factors, adhesion molecules, and chemokines are expressed in unique combinations by ECs of each organ. Furthermore, ECs respond distinctly in tissue regeneration models, hepatectomy, and myeloablation. To test the data set, we developed a transplantation model that employs generic ECs differentiated from embryonic stem cells. Transplanted generic ECs engraft into regenerating tissues and acquire features of organotypic ECs. Collectively, we demonstrate the utility of informational databases of ECs toward uncovering the extravascular and intrinsic signals that define EC heterogeneity. These factors could be exploited therapeutically to engineer tissue-specific ECs for regeneration.
微血管内皮细胞（ECs）在不同的组织中具有独特但尚未被认识的结构、表型和功能属性。我们设计了 EC 纯化、培养、分析和移植模型，建立了没有淋巴管内皮细胞或实质细胞的组织特异性 EC 分子文库。这些文库确定了赋予 EC 器官样特征的属性。我们表明，转录因子簇、血管生成生长因子、黏附分子和趋化因子在每个器官的 EC 中以独特的组合表达。此外，EC 在组织再生模型、肝切除术和骨髓清除术中反应明显不同。为了测试数据集，我们开发了一种移植模型，该模型使用从胚胎干细胞分化而来的通用 EC。移植的通用 EC 植入到再生组织中，并获得器官样 EC 的特征。总的来说，我们证明了 EC 信息数据库的实用性，它可以揭示定义 EC 异质性的血管外和内在信号。这些因素可以被利用来治疗性地设计用于组织特异性 EC 再生的工程。
