BACKGROUND As the population ages, an increasing number of postmenopausal women are donors of adipose stromal cells (ASCs) and may benefit from autologous ASC-related treatments. However, the effect of menopausal status on ASCs has not been investigated. METHODS RNA sequencing data were downloaded, and differentially expressed genes (DEGs) were identified. Hierarchical clustering, Gene Ontology, and pathway analyses were applied to the DEGs. Two gene coexpression network analysis approaches were applied to the DEGs to provide a holistic view and preserve gene interactions. Hub genes of the gene coexpression network were identified, and their expression profiles were examined with clinical samples. ASCs from pre- and postmenopausal women were co-cultured with monocytes and T cells to determine their immunoregulatory role. RESULTS In total, 2299 DEGs were identified and presented distinct expression profiles between pre- and postmenopausal women. Gene Ontology and pathway analyses revealed some fertility-, sex hormone-, immune-, aging-, and angiogenesis-related terms and pathways. Gene coexpression networks were constructed, and the top hub genes, including TIE1, ANGPT2, RNASE1, PLVAP, CA2, and MPZL2, were consistent between the two approaches. Expression profiles of hub genes from the RNA sequencing data and clinical samples were consistent. ASCs from postmenopausal women elicit M1 polarization, while their counterparts facilitate CD3/4+ T cell proliferation. CONCLUSIONS The present study reveals the transcriptome differences in ASCs derived from pre- and postmenopausal women and provides holistic views by preserving gene interactions via gene coexpression network analysis. The top hub genes identified by this study could serve as potential targets to enhance the therapeutic potential of ASCs.

中文翻译：

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绝经前和绝经后妇女的脂肪基质细胞的转录组差异。

背景技术随着人口的老龄化，越来越多的绝经后妇女是脂肪基质细胞（ASC）的供体，并且可能会受益于自体ASC相关治疗。但是，更年期状态对ASC的影响尚未得到研究。方法下载RNA测序数据，并鉴定差异表达基因（DEG）。分层聚类，基因本体论和途径分析被应用于DEG。将两种基因共表达网络分析方法应用于DEG，以提供整体视图并保留基因相互作用。鉴定了基因共表达网络的Hub基因，并用临床样品检查了它们的表达谱。将绝经前和绝经后妇女的ASC与单核细胞和T细胞共培养以确定其免疫调节作用。结果总计 在绝经前和绝经后妇女中鉴定出2299个DEG，并呈现出不同的表达特征。基因本体论和途径分析揭示了一些与生育，性激素，免疫，衰老和血管生成相关的术语和途径。构建了基因共表达网络，并且两种方法之间的最高集线器基因（包括TIE1，ANGPT2，RNASE1，PLVAP，CA2和MPZL2）保持一致。来自RNA测序数据和临床样品的中枢基因的表达谱是一致的。绝经后妇女的ASC引起M1极化，而它们的对应物则促进CD3 / 4 + T细胞增殖。结论本研究揭示了来自绝经前和绝经后妇女的ASCs的转录组差异，并通过基因共表达网络分析保留了基因相互作用，从而提供了整体观点。