Vascular Biology Program, Department of Surgery, Children’s Hospital Boston, Harvard Medical School, MA, USA.
Arterioscler Thromb Vasc Biol. 2011 Oct;31(10):2181-92. doi: 10.1161/ATVBAHA.111.232934. Epub 2011 Jul 14.
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 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.
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.
本研究旨在确定婴儿血管瘤（IH）中周细胞的细胞和分子起源及其在病理性血管形成中的功能作用。
本研究表明，IH 来源的干细胞（HemSCs）可形成周细胞样细胞。通过体外研究，我们证明 HemSC 向周细胞的分化取决于与内皮细胞的直接接触。成纤维细胞中异位表达 JAGGED1 足以诱导 HemSCs 获得周细胞样表型，表明 JAGGED1 起着关键作用。在体内，我们用重组 JAGGED1 阻断周细胞分化，观察到血管形成减少，周细胞明显缺乏。在内皮细胞中沉默 JAGGED1 减少了血管形成，导致周细胞数量减少。
本研究数据表明，内皮细胞 JAGGED1 控制了 IH 小鼠模型中 HemSC 向周细胞的分化，并提示周细胞在 IH 中血管形成中起着基础性作用。
