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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4777-4785.
Prepublished online as a Blood First Edition Paper on February 8, 2007; DOI 10.1182/blood-2006-10-053280.


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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment

Stefan Amatschek1,2, Ernst Kriehuber1,2, Wolfgang Bauer1,2, Barbel Reininger1,2, Paul Meraner3, Alois Wolpl3, Norbert Schweifer4, Christian Haslinger4, Georg Stingl2, and Dieter Maurer1,2

1 Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria; 2 Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Austria; 3 Laboratory of Medical Genetics, Martinsried, Germany; 4 Boehringer-Ingelheim Austria, Vienna, Austria

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.


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