| First Author | Swift J | Year | 2013 |
| Journal | Science | Volume | 341 |
| Issue | 6149 | Pages | 1240104 |
| PubMed ID | 23990565 | Mgi Jnum | J:201165 |
| Mgi Id | MGI:5511103 | Doi | 10.1126/science.1240104 |
| Citation | Swift J, et al. (2013) Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 341(6149):1240104 |
| abstractText | 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. |
