Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle-upon-Tyne, NE1 3BZ, UK.
The Blackett Laboratory, Imperial College London, London, SW7 2BW, UK.
Nat Commun. 2019 Apr 3;10(1):1496. doi: 10.1038/s41467-019-09331-6.
Whilst demonstrated extensively in vitro, the control of cell behaviour via modulation of substrate compliance in live tissues has not been accomplished to date. Here we propose that stem cells can be regulated solely through in situ modulation of tissue biomechanics. By first establishing, via high-resolution Brillouin spectro-microscopy, that the outer edge (limbus) of live human corneas has a substantially lower bulk modulus compared to their centre, we then demonstrate that this difference is associated with limbal epithelial stem cell (LESC) residence and YAP-dependent mechanotransduction. This phenotype-through-biomechanics correlation is further explored in vivo using a rabbit alkali burn model. Specifically, we show that treating the burnt surface of the cornea with collagenase effectively restores the tissue's mechanical properties and its capacity to support LESCs through mechanisms involving YAP suppression. Overall, these findings have extended implications for understanding stem cell niche biomechanics and its impact on tissue regeneration.
虽然在体外得到了广泛证实，但迄今为止，通过调节活组织中基质顺应性来控制细胞行为尚未实现。在这里，我们提出可以仅通过原位调节组织生物力学来调节干细胞。首先，通过高分辨率布里渊光谱显微镜证实，活的人眼角膜的外边缘（角膜缘）的体模量明显低于其中心，然后我们证明这种差异与角膜缘上皮干细胞（LESC）的驻留和 YAP 依赖性机械转导有关。使用兔碱烧伤模型进一步研究了这种表型-生物力学相关性。具体而言，我们表明，用胶原酶处理角膜烧伤表面可有效恢复组织的机械性能，并通过涉及 YAP 抑制的机制来支持 LESCs。总的来说，这些发现对于理解干细胞生态位生物力学及其对组织再生的影响具有重要意义。
