JAGGED1 signaling regulates hemangioma stem cell-to-pericyte/vascular smooth muscle cell differentiation.
JAGGED1 signaling regulates hemangioma stem cell-to-pericyte/vascular smooth muscle cell differentiation.
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DOI：
10.1161/atvbaha.111.232934
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Bischoff J
中科院分区：
文献类型：
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作者：
Boscolo E;Stewart CL;Greenberger S;Wu JK;Durham JT;Herman IM;Mulliken JB;Kitajewski J;Bischoff J
本研究的目的是确定婴儿血管瘤（IH）中周细胞的细胞和分子来源及其在病理血管形成中的功能作用。在这里，我们表明IH衍生的干细胞（HemSC）形成周细胞样细胞。在体外研究中，我们证明，造血干细胞的周细胞分化依赖于直接接触内皮细胞。在成纤维细胞中异位表达的JAGGED 1足以诱导HemSC获得周细胞样表型，表明JAGGED 1的关键作用。在体内，我们用重组JAGGED 1阻断周细胞分化，并观察到血管形成减少，周细胞明显缺乏。在内皮细胞中沉默JAGGED 1减少了血管形成，导致周细胞的缺乏。我们的数据表明，内皮JAGGED1控制HemSC的周细胞分化的小鼠模型的IH，并表明周细胞在血管的形成中的IH的基本作用。
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. 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 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. 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.