Laboratory of Biological Modeling, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
Section on Cellular Signaling, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland, USA.
Glia. 2023 Feb;71(2):205-228. doi: 10.1002/glia.24267. Epub 2022 Sep 12.
The mammalian pituitary gland is a complex organ consisting of hormone-producing cells, anterior lobe folliculostellate cells (FSCs), posterior lobe pituicytes, vascular pericytes and endothelial cells, and Sox2-expressing stem cells. We present single-cell RNA sequencing and immunohistofluorescence analyses of pituitary cells of adult female rats with a focus on the transcriptomic profiles of nonhormonal cell types. Samples obtained from whole pituitaries and separated anterior and posterior lobe cells contained all expected pituitary resident cell types and lobe-specific vascular cell subpopulations. FSCs and pituicytes expressed S100B, ALDOC, EAAT1, ALDH1A1, and VIM genes and proteins, as well as other astroglial marker genes, some common and some cell type-specific. We also found that the SOX2 gene and protein were expressed in ~15% of pituitary cells, including FSCs, pituicytes, and a fraction of hormone-producing cells, arguing against its stem cell specificity. FSCs comprised two Sox2-expressing subclusters; FS1 contained more cells but lower genetic diversity, while FS2 contained proliferative cells, shared genes with hormone-producing cells, and expressed genes consistent with stem cell niche formation, regulation of cell proliferation and stem cell pluripotency, including the Hippo and Wnt pathways. FS1 cells were randomly distributed in the anterior and intermediate lobes, while FS2 cells were localized exclusively in the marginal zone between the anterior and intermediate lobes. These data indicate the identity of the FSCs as anterior pituitary-specific astroglia, with FS1 cells representing differentiated cells equipped for classical FSC roles and FS2 cells exhibiting additional stem cell-like features.
哺乳动物垂体是一个由激素产生细胞、前叶滤泡星状细胞（FSCs）、后叶垂体细胞、血管周细胞和内皮细胞以及表达 Sox2 的干细胞组成的复杂器官。我们对成年雌性大鼠垂体细胞进行了单细胞 RNA 测序和免疫荧光分析，重点研究了非激素细胞类型的转录组谱。从整个垂体和分离的前叶和后叶细胞获得的样本包含了所有预期的垂体固有细胞类型和叶特异性血管细胞亚群。FSCs 和垂体细胞表达 S100B、ALDOC、EAAT1、ALDH1A1 和 VIM 基因和蛋白质，以及其他一些星形胶质细胞标记基因，有些是共同的，有些是细胞类型特异性的。我们还发现，SOX2 基因和蛋白质在约 15%的垂体细胞中表达，包括 FSCs、垂体细胞和一部分激素产生细胞，这表明其干细胞特异性值得怀疑。FSCs 包含两个表达 Sox2 的亚群；FS1 包含更多的细胞，但遗传多样性较低，而 FS2 包含增殖细胞、与激素产生细胞共享的基因，并表达与干细胞龛形成、细胞增殖调控和干细胞多能性一致的基因，包括 Hippo 和 Wnt 通路。FS1 细胞随机分布在前叶和中间叶，而 FS2 细胞仅局限于前叶和中间叶之间的边缘区。这些数据表明 FSCs 的身份是前垂体特异性星形胶质细胞，FS1 细胞代表具有经典 FSC 作用的分化细胞，FS2 细胞表现出额外的干细胞样特征。
