Oligodendrocytes produce and repair myelin, which is critical for the integrity and function of the central nervous system (CNS). Oligodendrocyte and oligodendrocyte progenitor cell (OPC) biology is modulated in vitro by mechanical cues within the magnitudes observed in vivo. In some cases, these cues are sufficient to accelerate or inhibit terminal differentiation of murine oligodendrocyte progenitors. However, our understanding of oligodendrocyte lineage mechanobiology has been restricted primarily to animal models to date, due to the inaccessibility and challenges of human oligodendrocyte cell culture. Here, we probe the mechanosensitivity of human oligodendrocyte lineage cells derived from human induced pluripotent stem cells. We target phenotypically distinct stages of the human oligodendrocyte lineage and quantify the effect of substratum stiffness on cell migration and differentiation, within the range documented in vivo. We find that human oligodendrocyte lineage cells exhibit mechanosensitive migration and differentiation. Further, we identify two patterns of human donor line-dependent mechanosensitive differentiation. Our findings illustrate the variation among human oligodendrocyte responses, otherwise not captured by animal models, that are important for translational research. Moreover, these findings highlight the importance of studying glia under conditions that better approximate in vivo mechanical cues. Despite significant progress in human oligodendrocyte derivation methodology, the extended duration, low yield, and low selectivity of human-induced pluripotent stem cell-derived oligodendrocyte protocols significantly limit the scale-up and implementation of these cells and protocols for in vivo and in vitro applications. We propose that mechanical modulation, in combination with traditional soluble and insoluble factors, provides a key avenue to address these challenges in cell production and in vitro analysis.

少突胶质细胞产生并修复髓磷脂，这对于中枢神经系统（CNS）的完整性和功能至关重要。少突胶质细胞和少突胶质细胞祖细胞 (OPC) 生物学调节体外通过观察到的幅度内的机械线索体内。在某些情况下，这些线索足以加速或抑制小鼠少突胶质细胞祖细胞的终末分化。然而，由于人类少突胶质细胞培养的困难和挑战，迄今为止，我们对少突胶质细胞谱系力学生物学的理解主要局限于动物模型。在这里，我们探讨了源自人类诱导多能干细胞的人类少突胶质细胞系细胞的机械敏感性。我们针对人类少突胶质细胞谱系的表型不同阶段，并在记录的范围内量化基质硬度对细胞迁移和分化的影响体内。我们发现人类少突胶质细胞系细胞表现出机械敏感性迁移和分化。此外，我们还确定了人类供体系依赖性机械敏感分化的两种模式。我们的研究结果说明了人类少突胶质细胞反应之间的差异，否则动物模型无法捕获这些差异，这对于转化研究非常重要。此外，这些发现强调了在更接近的条件下研究神经胶质细胞的重要性体内机械提示。尽管人少突胶质细胞衍生方法学取得了重大进展，但人诱导多能干细胞衍生的少突胶质细胞方案的持续时间延长、产量低和选择性低，严重限制了这些细胞和方案的规模化和实施。体内和体外应用程序。我们认为，机械调节与传统的可溶性和不溶性因子相结合，为解决细胞生产和生产中的这些挑战提供了关键途径。体外分析。