Jiangxi Provincial Key Laboratory of Systems Biomedicine, Jiujiang University, Jiujiang, China.
J Cell Physiol. 2020 Jan;235(1):349-363. doi: 10.1002/jcp.28974. Epub 2019 Jun 25.
Metabolism homeostasis plays an important role in progenitor-cell differentiation to adipocytes, but less is known about the whole transcriptional profiling of cellular metabolism during adipogenesis. We got the first insight into the whole transcriptional profiling of cellular metabolism during adipogenesis from human mesenchymal stem cells (hMSCs) by the RNA-Seq technique. There were 1,998, 2,629, 3,112, and 3,054 differentially expressed genes (DEGs) at Days 7, 14, 21, and 28, respectively, during adipogenesis. The most enriched phosphatidylinositol 3' kinase-serine/threonine kinase (PI3K-Akt) signaling pathway stimulated and directly regulated cellular metabolism by priming glucose aerobic glycolysis, arginine and proline metabolism, glutathione metabolism, and arachidonic acid metabolism during adipogenesis, targeting the potential key genes, such as fatty acid synthase (FABP4), phosphoenolpyruvate carboxykinase 1 (PKC1), stearoyl-CoA desaturase (SCD), and solute carrier family 2 member 1 of Gluts (SLC2A1). And it confirmed PCK1 as the key player for cellular metabolism by small interfering RNA. A comprehensive understanding of cellular metabolism and its regulatory axis of the signaling pathway during adipogenesis would reveal new study and therapy targets for fat metabolism disorders.
代谢平衡在祖细胞向脂肪细胞分化中起着重要作用,但在脂肪生成过程中,细胞代谢的全转录组谱知之甚少。我们通过 RNA-Seq 技术首次深入了解了人骨髓间充质干细胞 (hMSC) 脂肪生成过程中的细胞代谢全转录组谱。在脂肪生成过程中,分别有 1998、2629、3112 和 3054 个差异表达基因 (DEG) 在第 7、14、21 和 28 天表达。在脂肪生成过程中,最丰富的磷脂酰肌醇 3' 激酶-丝氨酸/苏氨酸激酶 (PI3K-Akt) 信号通路通过启动葡萄糖有氧糖酵解、精氨酸和脯氨酸代谢、谷胱甘肽代谢和花生四烯酸代谢来刺激和直接调节细胞代谢,针对潜在的关键基因,如脂肪酸合酶 (FABP4)、磷酸烯醇丙酮酸羧激酶 1 (PKC1)、硬脂酰辅酶 A 去饱和酶 (SCD) 和谷氨酸盐载体家族 2 成员 1 (SLC2A1)。并通过小干扰 RNA 证实 PCK1 是细胞代谢的关键因子。全面了解脂肪生成过程中的细胞代谢及其信号通路的调节轴,将为脂肪代谢紊乱的新研究和治疗靶点提供启示。