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. METHODS AND 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.
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. METHODS AND 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: J Yamashita; H Itoh; M Hirashima; M Ogawa; S Nishikawa; T Yurugi; M Naito; K Nakao; S Nishikawa Journal: Nature Date: 2000-11-02 Impact factor: 49.962
Authors: Sulochana S Bhandarkar; Marisa Jaconi; Levi E Fried; Michael Y Bonner; Benjamin Lefkove; Baskaran Govindarajan; Betsy N Perry; Ravi Parhar; Jamie Mackelfresh; Allie Sohn; Michael Stouffs; Ulla Knaus; George Yancopoulos; Yvonne Reiss; Andrew V Benest; Hellmut G Augustin; Jack L Arbiser Journal: J Clin Invest Date: 2009-07-13 Impact factor: 14.808
Authors: June K Wu; Omotinuwe Adepoju; Dinuka De Silva; Keith Baribault; Elisa Boscolo; Joyce Bischoff; Jan Kitajewski Journal: Angiogenesis Date: 2010-01-13 Impact factor: 9.596
Authors: David M Smadja; Coralie L Guerin; Elisa Boscolo; Ivan Bieche; John B Mulliken; Joyce Bischoff Journal: Stem Cells Date: 2014-03 Impact factor: 6.277
Authors: Andrew K Edwards; Kyle Glithero; Peter Grzesik; Alison A Kitajewski; Naikhoba Co Munabi; Krista Hardy; Qian Kun Tan; Michael Schonning; Thaned Kangsamaksin; Jan K Kitajewski; Carrie J Shawber; June K Wu Journal: JCI Insight Date: 2017-11-02