Chen Pengyu, Song Mingrui, Wang Yutian, Deng Songyun, Hong Weisheng, Zhang Xianrong, Yu Bin
Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
PeerJ. 2020 Jul 21;8:e9484. doi: 10.7717/peerj.9484. eCollection 2020.
Bone marrow adipocyte (BMA), closely associated with bone degeneration, shares common progenitors with osteoblastic lineage. However, the intrinsic mechanism of cells fate commitment between BMA and osteogenic lineage remains unclear.
Gene Expression Omnibus (GEO) dataset GSE107789 publicly available was downloaded and analyzed. Differentially expressed genes (DEGs) were analyzed using GEO2R. Functional and pathway enrichment analyses of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were conducted by The Database for Annotation, Visualization and Integrated Discovery and Gene set enrichment analysis software. Protein-protein interactions (PPI) network was obtained using STRING database, visualized and clustered by Cytoscape software. Transcriptional levels of key genes were verified by real-time quantitative PCR in vitro in Bone marrow stromal cells (BMSCs) undergoing adipogenic differentiation at day 7 and in vivo in ovariectomized mice model.
A total of 2,869 DEGs, including 1,357 up-regulated and 1,512 down-regulated ones, were screened out from transcriptional profile of human BMSCs undergoing adipogenic induction at day 7 vs. day 0. Functional and pathway enrichment analysis, combined with modules analysis of PPI network, highlighted ACSL1, sphingosine 1-phosphate receptors 3 (S1PR3), ZBTB16 and glypican 3 as key genes up-regulated at the early stage of BMSCs adipogenic differentiation. Furthermore, up-regulated mRNA expression levels of ACSL1, S1PR3 and ZBTB16 were confirmed both in vitro and in vivo.
ACSL1, S1PR3 and ZBTB16 may play crucial roles in early regulation of BMSCs adipogenic differentiation.
骨髓脂肪细胞（BMA）与骨退化密切相关，与成骨细胞系具有共同的祖细胞。然而，BMA与成骨细胞系之间细胞命运决定的内在机制仍不清楚。
下载并分析公开可用的基因表达综合数据库（GEO）数据集GSE107789。使用GEO2R分析差异表达基因（DEG）。通过注释、可视化和综合发现数据库以及基因集富集分析软件对基因本体论和京都基因与基因组百科全书进行功能和通路富集分析。使用STRING数据库获得蛋白质-蛋白质相互作用（PPI）网络，通过Cytoscape软件进行可视化和聚类。通过实时定量PCR在体外对第7天进行脂肪生成分化的骨髓基质细胞（BMSC）以及在体内对去卵巢小鼠模型中关键基因的转录水平进行验证。
从第7天与第0天进行脂肪生成诱导的人BMSC转录谱中筛选出总共2869个DEG，其中包括1357个上调基因和1512个下调基因。功能和通路富集分析，结合PPI网络的模块分析，突出显示ACSL1、鞘氨醇-1-磷酸受体3（S1PR3）、ZBTB16和磷脂酰肌醇蛋白聚糖3是在BMSC脂肪生成分化早期上调的关键基因。此外，在体外和体内均证实了ACSL1、S1PR3和ZBTB16的mRNA表达水平上调。
ACSL1、S1PR3和ZBTB16可能在BMSC脂肪生成分化的早期调节中起关键作用。
