title: Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment.
abstract: 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.
authors.affiliation: Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Amatschek
authors.forename: Ernst
authors.initials: E
authors.lastname: Kriehuber
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bauer
authors.forename: Barbel
authors.initials: B
authors.lastname: Reininger
authors.forename: Paul
authors.initials: P
authors.lastname: Meraner
authors.forename: Alois
authors.initials: A
authors.lastname: Wolpl
authors.forename: Norbert
authors.initials: N
authors.lastname: Schweifer
authors.forename: Christian
authors.initials: C
authors.lastname: Haslinger
authors.forename: Georg
authors.initials: G
authors.lastname: Stingl
authors.forename: Dieter
authors.initials: D
authors.lastname: Maurer
mesh_terms: D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D020869:Gene Expression Profiling; D016678:Genome; D000949:Histocompatibility Antigens Class II / Q000737:chemistry; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D008833:Microcirculation; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000737:chemistry; D014158:Transcription, Genetic
chemical_list: D000949:Histocompatibility Antigens Class II; D010455:Peptides