title: Transcript analysis reveals a specific HOX signature associated with positional identity of human endothelial cells.
abstract: The endothelial cell has a remarkable ability for sub-specialisation, adapted to the needs of a variety of vascular beds. The role of developmental programming versus the tissue contextual environment for this specialization is not well understood. Here we describe a hierarchy of expression of HOX genes associated with endothelial cell origin and location. In initial microarray studies, differential gene expression was examined in two endothelial cell lines: blood derived outgrowth endothelial cells (BOECs) and pulmonary artery endothelial cells. This suggested shared and differential patterns of HOX gene expression between the two endothelial lines. For example, this included a cluster on chromosome 2 of HOXD1, HOXD3, HOXD4, HOXD8 and HOXD9 that was expressed at a higher level in BOECs. Quantative PCR confirmed the higher expression of these HOXs in BOECs, a pattern that was shared by a variety of microvascular endothelial cell lines. Subsequently, we analysed publically available microarrays from a variety of adult cell and tissue types using the whole "HOX transcriptome" of all 39 HOX genes. Using hierarchical clustering analysis the HOX transcriptome was able to discriminate endothelial cells from 61 diverse human cell lines of various origins. In a separate publically available microarray dataset of 53 human endothelial cell lines, the HOX transcriptome additionally organized endothelial cells related to their organ or tissue of origin. Human tissue staining for HOXD8 and HOXD9 confirmed endothelial expression and also supported increased microvascular expression of these HOXs. Together these observations suggest a significant involvement of HOX genes in endothelial cell positional identity.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom; Papworth Hospital, Cambridge, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Toshner
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Dunmore
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Eoin F
authors.initials: EF
authors.lastname: McKinney
authors.affiliation: Papworth Hospital, Cambridge, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Southwood
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Paola
authors.initials: P
authors.lastname: Caruso
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Upton
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: John P
authors.initials: JP
authors.lastname: Waters
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Ormiston
authors.affiliation: Department of Physiology and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Skepper
authors.affiliation: School of Clinical and Experimental Medicine, Birmingham University, Birmingham, United Kingdom.
authors.forename: Gerard
authors.initials: G
authors.lastname: Nash
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Amer A
authors.initials: AA
authors.lastname: Rana
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Morrell
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D005333:Fetus / Q000196:embryology / Q000378:metabolism; D020869:Gene Expression Profiling; D063990:Gene Ontology; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000196:embryology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D011651:Pulmonary Artery / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger