Molecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science. 2013 Aug 30;341(6149):1240104. doi: 10.1126/science.1240104.
Tissues can be soft like fat, which bears little stress, or stiff like bone, which sustains high stress, but whether there is a systematic relationship between tissue mechanics and differentiation is unknown. Here, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, E, as did levels of collagens in the extracellular matrix that determine E. Stem cell differentiation into fat on soft matrix was enhanced by low lamin-A levels, whereas differentiation into bone on stiff matrix was enhanced by high lamin-A levels. Matrix stiffness directly influenced lamin-A protein levels, and, although lamin-A transcription was regulated by the vitamin A/retinoic acid (RA) pathway with broad roles in development, nuclear entry of RA receptors was modulated by lamin-A protein. Tissue stiffness and stress thus increase lamin-A levels, which stabilize the nucleus while also contributing to lineage determination.
组织可以像脂肪一样柔软，承受的压力很小，也可以像骨骼一样坚硬，承受很高的压力，但组织力学和分化之间是否存在系统关系尚不清楚。在这里，蛋白质组学分析表明，核骨架蛋白核纤层蛋白 A 的水平与组织弹性 E 呈比例关系，细胞外基质中决定 E 的胶原水平也是如此。在柔软的基质上，干细胞向脂肪的分化会因低水平的核纤层蛋白 A 而增强，而在坚硬的基质上向骨的分化则会因高水平的核纤层蛋白 A 而增强。基质的硬度直接影响核纤层蛋白 A 的水平，尽管核纤层蛋白 A 的转录受维生素 A/视黄酸 (RA) 途径调控，该途径在发育中具有广泛的作用，但 RA 受体的核内进入受到核纤层蛋白 A 的调节。因此，组织的硬度和应力会增加核纤层蛋白 A 的水平，在稳定核的同时也有助于谱系决定。
