关键词: Hic1 Blood brain barrier Choroid plexus Fibroblasts Meninges Mesenchymal cells Neurovascular Pericytes Pituitary scRNA-seq

Mesh : Mice Animals Mesenchymal Stem Cells Blood-Brain Barrier / metabolism Fibroblasts Single-Cell Analysis Choroid Plexus / metabolism Red Fluorescent Protein

来  源:   DOI:10.1186/s12987-024-00535-7   PDF(Pubmed)

Abstract:
BACKGROUND: In the choroid plexus and pituitary gland, vasculature is known to have a permeable, fenestrated phenotype which allows for the free passage of molecules in contrast to the blood brain barrier observed in the rest of the CNS. The endothelium of these compartments, along with secretory, neural-lineage cells (choroid epithelium and pituitary endocrine cells) have been studied in detail, but less attention has been given to the perivascular mesenchymal cells of these compartments.
METHODS: The Hic1CreERT2 Rosa26LSL-TdTomato mouse model was used in conjunction with a PdgfraH2B-EGFP mouse model to examine mesenchymal cells, which can be subdivided into Pdgfra+ fibroblasts and Pdgfra- pericytes within the choroid plexus (CP) and pituitary gland (PG), by histological, immunofluorescence staining and single-cell RNA-sequencing analyses.
RESULTS: We found that both CP and PG possess substantial populations of distinct Hic1+ mesenchymal cells, including an abundance of Pdgfra+ fibroblasts. Within the pituitary, we identified distinct subpopulations of Hic1+ fibroblasts in the glandular anterior pituitary and the neurosecretory posterior pituitary. We also identified multiple distinct markers of CP, PG, and the meningeal mesenchymal compartment, including alkaline phosphatase, indole-n-methyltransferase and CD34.
CONCLUSIONS: Novel, distinct subpopulations of mesenchymal cells can be found in permeable vascular interfaces, including the CP, PG, and meninges, and make distinct contributions to both organs through the production of structural proteins, enzymes, transporters, and trophic molecules.
摘要:
背景:在脉络丛和垂体中,已知脉管系统具有渗透性,与在CNS的其余部分中观察到的血脑屏障相反,允许分子自由通过的开窗表型。这些隔室的内皮,随着分泌,神经谱系细胞(脉络膜上皮和垂体内分泌细胞)已被详细研究,但是对这些区室的血管周围间充质细胞的关注较少。
方法:将Hic1CreERT2Rosa26LSL-TdTomato小鼠模型与PdgfraH2B-EGFP小鼠模型结合使用,以检查间充质细胞,可细分为脉络丛(CP)和垂体(PG)内的Pdgfra成纤维细胞和Pdgfra-周细胞,通过组织学,免疫荧光染色和单细胞RNA测序分析。
结果:我们发现CP和PG都拥有大量不同的Hic1+间充质细胞,包括丰富的Pdgfra+成纤维细胞。在垂体内,我们在腺性垂体前叶和神经分泌型垂体后叶确定了不同的Hic1+成纤维细胞亚群.我们还确定了CP的多个不同标记,PG,和脑膜间充质室,包括碱性磷酸酶,吲哚-n-甲基转移酶和CD34。
结论:新颖,间充质细胞的不同亚群可以在可渗透的血管界面中发现,包括CP,PG,和脑膜,并通过产生结构蛋白对两个器官做出不同的贡献,酶,运输商,和营养分子。
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