title: JAGGED1 signaling regulates hemangioma stem cell-to-pericyte/vascular smooth muscle cell differentiation.
abstract: OBJECTIVE
  The aim of our study is to determine the cellular and molecular origin for the pericytes in infantile hemangioma (IH) and their functional role in the formation of pathological blood vessels.
  
  
  RESULTS
  Here we show that IH-derived stem cells (HemSCs) form pericyte-like cells. With in vitro studies, we demonstrate that HemSC-to-pericyte differentiation depends on direct contact with endothelial cells. JAGGED1 expressed ectopically in fibroblasts was sufficient to induce HemSCs to acquire a pericyte-like phenotype, indicating a critical role for JAGGED1. In vivo, we blocked pericyte differentiation with recombinant JAGGED1, and we observed reduced formation of blood vessels, with an evident lack of pericytes. Silencing JAGGED1 in the endothelial cells reduced blood vessel formation and resulted in a paucity of pericytes.
  
  
  CONCLUSIONS
  Our data show that endothelial JAGGED1 controls HemSC-to-pericyte differentiation in a murine model of IH and suggests that pericytes have a fundamental role in formation of blood vessels in IH.
authors.affiliation: Vascular Biology Program, Department of Surgery, Children’s Hospital Boston, Harvard Medical School, MA, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Boscolo
authors.forename: Camille L
authors.initials: CL
authors.lastname: Stewart
authors.forename: Shoshana
authors.initials: S
authors.lastname: Greenberger
authors.forename: June K
authors.initials: JK
authors.lastname: Wu
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Durham
authors.forename: Ira M
authors.initials: IM
authors.lastname: Herman
authors.forename: John B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: Jan
authors.initials: J
authors.lastname: Kitajewski
authors.forename: Joyce
authors.initials: J
authors.lastname: Bischoff
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism; D006391:Hemangioma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D020286:Pericytes / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011994:Recombinant Proteins; D000072099:Serrate-Jagged Proteins