Laboratory of Anatomy and Cell Biology, Department of Health Sciences, Kyorin University, 5-4-1 Shimorenjaku, Mitaka, Tokyo, 181-8612, Japan.
Institute for Endocrinology, Meiji University, 1-1-1 Higashi-mita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan.
Histochem Cell Biol. 2020 Jun;153(6):385-396. doi: 10.1007/s00418-020-01862-0. Epub 2020 Mar 9.
Approximately 8% of CD9-, S100β- and SOX2-triple positive (CD9/S100β/SOX2-positive) stem/progenitor cells in the anterior lobe of the rat pituitary gland have previously been shown to differentiate into endothelial cells in vitro, suggesting that they play a role in vascularisation as tissue-resident vascular precursor cells. In the present study, we focused on chemokine ligands to further characterise the CD9/S100β/SOX2-positive cells and found that they distinctively express CX3C chemokine ligand 1 (Cx3cl1). Immunohistochemical analysis of the anterior lobe showed that CX3CL1-positive cells comprised 7.8% in CD9-positive cells. By cultivation of the CD9-positive cells on laminin-coated plates, we observed that the expression levels of Cx3cl1 decreased, while those of Sox18, an endothelial cell-progenitor marker, and Cx3cr1, a CX3CL1 receptor, increased. Furthermore, in a rat model of prolactinoma, the most common pituitary tumour, which is accompanied by frequent neo-vasculogenesis in the anterior lobe, we have confirmed a decrease in Cx3cl1 expression and an increase in Cx3cr1 expression, as well as a prominent increase in Sox18 expression. These findings suggest that CX3CL1/CX3CR1 signalling in CD9/S100β/SOX2-positive cells plays an important role in resupplying endothelial cells for vascular remodelling in the anterior lobe.
先前已经证明，大鼠垂体前叶中约 8%的 CD9、S100β 和 SOX2 三重阳性（CD9/S100β/SOX2-阳性）干细胞/祖细胞能够在体外分化为内皮细胞，这表明它们作为组织驻留的血管前体细胞在血管生成中发挥作用。在本研究中，我们专注于趋化因子配体，以进一步表征 CD9/S100β/SOX2-阳性细胞，发现它们特异表达 CX3C 趋化因子配体 1（Cx3cl1）。对垂体前叶的免疫组织化学分析表明，CX3CL1 阳性细胞占 CD9 阳性细胞的 7.8%。通过在层粘连蛋白包被的平板上培养 CD9 阳性细胞，我们观察到 Cx3cl1 的表达水平降低，而 Sox18（内皮细胞祖细胞标志物）和 Cx3cr1（CX3CL1 受体）的表达水平增加。此外，在催乳素瘤（最常见的垂体肿瘤）大鼠模型中，前叶常伴有新生血管生成，我们已经证实 Cx3cl1 的表达降低，Cx3cr1 的表达增加，以及 Sox18 的表达明显增加。这些发现表明，CD9/S100β/SOX2-阳性细胞中的 CX3CL1/CX3CR1 信号通路在为前叶的血管重塑提供内皮细胞方面发挥着重要作用。
