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Functional analysis and transcriptome profile of meninges and skin fibroblasts from human‐aged donors
Cell Proliferation ( IF 8.5 ) Pub Date : 2024-02-29 , DOI: 10.1111/cpr.13627
Valentina Fantini 1 , Riccardo Rocco Ferrari 1 , Matteo Bordoni 2 , Eleonora Spampinato 2, 3 , Cecilia Pandini 4, 5 , Annalisa Davin 1 , Valentina Medici 6 , Stella Gagliardi 4 , Antonio Guaita 1, 6 , Orietta Pansarasa 2 , Cristina Cereda 7 , Tino Emanuele Poloni 6, 8
Affiliation  

The central nervous system (CNS) is surrounded by three membranes called meninges. Specialised fibroblasts, originating from the mesoderm and neural crest, primarily populate the meninges and serve as a binding agent. Our goal was to compare fibroblasts from meninges and skin obtained from the same human‐aged donors, exploring their molecular and cellular characteristics related to CNS functions. We isolated meningeal fibroblasts (MFs) from brain donors and skin fibroblasts (SFs) from the same subjects. A functional analysis was performed measuring cell appearance, metabolic activity, and cellular orientation. We examined fibronectin, serpin H1, β‐III‐tubulin, and nestin through qPCR and immunofluorescence. A whole transcriptome analysis was also performed to characterise the gene expression of MFs and SFs. MFs appeared more rapidly in the post‐tissue processing, while SFs showed an elevated cellular metabolism and a well‐defined cellular orientation. The four markers were mostly similar between the MFs and SFs, except for nestin, more expressed in MFs. Transcriptome analysis reveals significant differences, particularly in cyclic adenosine monophosphate (cAMP) metabolism and response to forskolin, both of which are upregulated in MFs. This study highlights MFs' unique characteristics, including the timing of appearance, metabolic activity, and gene expression patterns, particularly in cAMP metabolism and response to forskolin. These findings contribute to a deeper understanding of non‐neuronal cells' involvement in CNS activities and potentially open avenues for therapeutic exploration.

中文翻译:

人类老年供体脑膜和皮肤成纤维细胞的功能分析和转录组谱

中枢神经系统 (CNS) 由三层膜(称为脑膜)包围。源自中胚层和神经嵴的特殊成纤维细胞主要填充在脑膜中并充当结合剂。我们的目标是比较从相同年龄的人类捐赠者获得的脑膜和皮肤的成纤维细胞,探索它们与中枢神经系统功能相关的分子和细胞特征。我们从脑供体中分离出脑膜成纤维细胞(MF),并从同一受试者中分离出皮肤成纤维细胞(SF)。进行功能分析,测量细胞外观、代谢活性和细胞方向。我们通过 qPCR 和免疫荧光检查了纤连蛋白、丝氨酸蛋白酶抑制剂 H1、β-III-微管蛋白和巢蛋白。还进行了全转录组分析来表征 MF 和 SF 的基因表达。MF 在组织后处理中出现得更快,而 SF 则表现出更高的细胞代谢和明确的细胞方向。MF 和 SF 之间的四个标记大多相似,除了巢蛋白在 MF 中表达更多。转录组分析揭示了显着差异,特别是在环磷酸腺苷 (cAMP) 代谢和对毛喉素的反应方面,两者在 MF 中均上调。这项研究强调了 MF 的独特特征,包括出现时间、代谢活动和基因表达模式,特别是 cAMP 代谢和对毛喉素的反应。这些发现有助于更深入地了解非神经元细胞参与中枢神经系统活动,并可能为治疗探索开辟途径。
更新日期:2024-02-29
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