期刊
DEVELOPMENTAL CELL
卷 26, 期 2, 页码 204-219出版社
CELL PRESS
DOI: 10.1016/j.devcel.2013.06.017
关键词
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资金
- Ansary Stem Cell Institute
- Howard Hughes Medical Institute
- Empire State Stem Cell Board
- New York State Department of Health [NYSTEM C024180, C026438, C026878]
- NHLBI [R01 HL097797, R01 DK095039]
- Qatar National Priorities Research Foundation [NPRP08-663-3-140, NPRP09-1087-3-274]
- Qatar Foundation BioMedical Research Program (BMRP)
- Tri-Institutional Weill Cornell Starr Stem Cell Scholar program
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.
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