From the Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University (I.O., L.W., G.H., J.Z.).
Department of Cardiology, The First Affiliated Hospital of Nanchang University, Jiangxi, China (L.W., Z.Z.).
Arterioscler Thromb Vasc Biol. 2020 May;40(5):1231-1238. doi: 10.1161/ATVBAHA.120.314078. Epub 2020 Mar 12.
While GFAP (glial fibrillary acidic protein) is commonly used as a classical marker for astrocytes in the central nervous system, GFAP-expressing progenitor cells give rise to other cell types during development. The goal of this study was to investigate whether GFAP-expressing progenitor cells contribute to the development of vascular cells in major arteries. Approach and Results: To label GFAP-expressing progenitor cells and their progeny, we crossed promoter-driven recombinase mice (-) with transgenic mice expressing the -dependent dual fluorescent reporter gene. Using this genetic fate-mapping approach, here we demonstrate that GFAP-positive progenitor cells contribute to the development of vascular smooth muscle cells in both neural crest- and non-neural crest-derived vascular beds. In addition, GFAP-positive progenitor cells contribute to a subset of endothelial cells in some vasculature. Furthermore, fate-mapping analyses at multiple time points of mouse development demonstrate a time-dependent increase in the contribution of GFAP-positive progenitors to vascular smooth muscle cells, which mostly occurs in the postnatal period.
Our study demonstrates that vascular smooth muscle cells and endothelial cells within the same vascular segment are developmentally heterogeneous, where varying proportions of vascular smooth muscle cells and endothelial cells are contributed by GFAP-positive progenitor cells.
胶质纤维酸性蛋白(GFAP)通常被用作中枢神经系统中星形胶质细胞的经典标志物,但 GFAP 表达祖细胞在发育过程中会产生其他细胞类型。本研究旨在探讨 GFAP 表达祖细胞是否有助于大血管中血管细胞的发育。
为了标记表达 GFAP 的祖细胞及其后代,我们将启动子驱动的重组酶小鼠(-/-)与表达依赖的双荧光报告基因的转基因小鼠杂交。使用这种遗传谱系追踪方法,我们在此证明 GFAP 阳性祖细胞有助于神经嵴和非神经嵴来源的血管床中血管平滑肌细胞的发育。此外,GFAP 阳性祖细胞有助于一些血管中的一部分内皮细胞。此外,对小鼠发育的多个时间点的谱系追踪分析表明,GFAP 阳性祖细胞对血管平滑肌细胞的贡献随时间呈依赖性增加,主要发生在出生后时期。
我们的研究表明,同一血管段内的血管平滑肌细胞和内皮细胞在发育上是异质的,其中 GFAP 阳性祖细胞对血管平滑肌细胞和内皮细胞的贡献比例不同。