A transcriptional regulatory network connects mitochondrial biogenesis and metabolic shift with stem cell commitment to hepatic differentiation

Mitochondrial biogenesis and metabolism recently emerged as critical modulators of stemness properties and differentiation programmes. The increase in mitochondrial biogenesis and metabolic shift toward increased oxidative phosphorylations (OXPHOS) appear as hallmarks of stem cell differentiation processes. While several mechanisms support the involvement of mitochondrial biogenesis and function in the regulation of stem cell differentiation, the mechanisms triggering mitochondrial biogenesis in the context of cell differentiation remain elusive. In this study, we performed transcriptomic and bioinformatic analyses in order to get deeper insights into the cross-regulation of mitochondrial biogenesis and hepatogenic differentiation of human bone marrow mesenchymal stem cells (BM-MSCs). We identified a transcriptional regulatory network involved in the co-regulation of stem cell differentiation and mitochondrial biogenesis.

近期研究表明，线粒体生物发生（mitochondrial biogenesis）与代谢过程是调控干细胞干性特征与分化程序的关键介导因子。线粒体生物发生的增强以及向氧化磷酸化（OXPHOS）增强方向的代谢重编程，是干细胞分化进程的标志性特征。尽管已有多项机制证实线粒体生物发生与功能参与调控干细胞分化，但在细胞分化背景下触发线粒体生物发生的具体机制仍不明晰。本研究针对人骨髓间充质干细胞（BM-MSCs），通过转录组学与生物信息学分析，深入解析了线粒体生物发生与肝向分化之间的交叉调控机制，并最终鉴定出一套协同调控干细胞分化与线粒体生物发生的转录调控网络。