Zheng, YingChoi, Yoon Jung2019-02-222019-02-222018Choi_washington_0250E_19430.pdfhttp://hdl.handle.net/1773/43302Thesis (Ph.D.)--University of Washington, 2018For a long time, the endothelium was considered to be a homogenous passive surface that existed primarily to support blood flow. In recent decades, however, both the heterogeneity of the endothelium and its importance in supporting organ-specific function have been increasingly recognized. Endothelial cells from different vascular beds have been shown to differ markedly, both across the arterial, venous, and lymphatic systems of the large vasculature, as well as between the microvascular beds of different organs. Endothelial cells themselves are now known to communicate with surrounding parenchymal tissue, and thereby to play an important role in non-vascular organ development and function. In vivo studies have provided extensive knowledge of organ-specific vascular heterogeneity; however, these studies have predominantly been performed in murine models and may not be directly applicable to human biology or the development of human therapeutics. To date, very few works have studied organ-specific endothelial functions and their underlying molecular mechanisms. The following dissertation reports on the properties of endothelial cells isolated from four major human organs—the heart, lung, liver, and kidneys—in individual fetal tissues at three months’ gestation, at structural, gene expression, and cellular functional levels. After characterizing differences across organ vascular beds, this research next explores liver endothelial specific contributions to fetal liver hematopoiesis. We replicated the human fetal vascular niche in vitro and investigated the role of WNT5A in supporting hematopoiesis. Overall, these studies provide a "library" of information about the different characteristics of organ-specific endothelial cells, and report on the creation of organotypic endothelial cell lines with in vitro stability. These findings, and the cell lines described, can be directly applied to future mechanistic studies within the fields of tissue engineering and regenerative medicine.application/pdfen-USCC BYBiomedical engineeringBioengineeringThesis