Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea.
Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea.
Cells. 2024 Nov 18;13(22):1905. doi: 10.3390/cells13221905.
ECM stiffness significantly influences the differentiation of adipose-derived stem cells (ADSCs), with YAP-a key transcription factor in the Hippo signaling pathway-playing a pivotal role. This study investigates the effects of ECM stiffness on ADSC differentiation and its relationship with YAP signaling. Various hydrogel concentrations were employed to simulate different levels of ECM stiffness, and their impact on ADSC differentiation was assessed through material properties, adipocyte-specific gene expression, lipid droplet staining, YAP localization, and protein levels. Our results demonstrated that increasing hydrogel stiffness enhanced adipocyte differentiation in a gradient manner. Notably, inhibiting YAP signaling further increased lipid droplet accumulation, suggesting that ECM stiffness influences adipogenesis by modulating YAP signaling and its cytoplasmic phosphorylation. This study elucidates the molecular mechanisms underlying ECM stiffness-dependent lipid deposition, highlighting YAP's regulatory role in adipogenesis. These findings provide valuable insights into the regulation of cell differentiation and have important implications for tissue engineering and obesity treatment strategies.
细胞外基质（ECM）硬度显著影响脂肪来源干细胞（ADSCs）的分化，YAP——Hippo 信号通路中的关键转录因子——在其中发挥着关键作用。本研究旨在探讨 ECM 硬度对 ADSC 分化的影响及其与 YAP 信号通路的关系。通过使用不同浓度的水凝胶来模拟不同硬度的 ECM，并通过材料特性、脂肪细胞特异性基因表达、脂滴染色、YAP 定位和蛋白水平来评估其对 ADSC 分化的影响。研究结果表明，水凝胶硬度的增加以梯度方式促进了脂肪细胞的分化。值得注意的是，抑制 YAP 信号通路进一步增加了脂滴的积累，这表明 ECM 硬度通过调节 YAP 信号通路及其细胞质磷酸化来影响脂肪生成。本研究阐明了 ECM 硬度依赖性脂质沉积的分子机制，突出了 YAP 在脂肪生成中的调节作用。这些发现为细胞分化的调控提供了有价值的见解，并对组织工程和肥胖治疗策略具有重要意义。
