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Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration.

TitleMolecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration.
Publication TypeJournal Article
Year of Publication2013
AuthorsNolan DJ, Ginsberg M, Israely E, Palikuqi B, Poulos MG, James D, Ding B-S, Schachterle W, Liu Y, Rosenwaks Z, Butler JM, Xiang J, Rafii A, Shido K, Rabbany SY, Elemento O, Rafii S
JournalDev Cell
Volume26
Issue2
Pagination204-19
Date Published2013 Jul 29
ISSN1878-1551
KeywordsAnimals, Cell Adhesion Molecules, Cell Differentiation, Cells, Cultured, Chemokines, Embryonic Stem Cells, Endothelial Cells, Humans, Intercellular Signaling Peptides and Proteins, Mice, Microvessels, Regeneration, Transcription Factors
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.

DOI10.1016/j.devcel.2013.06.017
Alternate JournalDev. Cell
PubMed ID23871589
PubMed Central IDPMC3873200
Grant ListDK095039 / DK / NIDDK NIH HHS / United States
R01 DK095039 / DK / NIDDK NIH HHS / United States
R01 HL097797 / HL / NHLBI NIH HHS / United States
R01S HL097797 / HL / NHLBI NIH HHS / United States
U01 HL066952 / HL / NHLBI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States