title: Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration.
abstract: 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.
authors.affiliation: Department of Genetic Medicine, Howard Hughes Medical Institute, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Nolan
authors.forename: Michael
authors.initials: M
authors.lastname: Ginsberg
authors.forename: Edo
authors.initials: E
authors.lastname: Israely
authors.forename: Brisa
authors.initials: B
authors.lastname: Palikuqi
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poulos
authors.forename: Daylon
authors.initials: D
authors.lastname: James
authors.forename: Bi-Sen
authors.initials: BS
authors.lastname: Ding
authors.forename: William
authors.initials: W
authors.lastname: Schachterle
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Zev
authors.initials: Z
authors.lastname: Rosenwaks
authors.forename: Jason M
authors.initials: JM
authors.lastname: Butler
authors.forename: Jenny
authors.initials: J
authors.lastname: Xiang
authors.forename: Arash
authors.initials: A
authors.lastname: Rafii
authors.forename: Koji
authors.initials: K
authors.lastname: Shido
authors.forename: Sina Y
authors.initials: SY
authors.lastname: Rabbany
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D055806:Microvessels / Q000378:metabolism; D012038:Regeneration; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D014157:Transcription Factors