Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation

Joe Swift, Irena L. Ivanovska, Amnon Buxboim, Takamasa Harada, P. C Dave P Dingal, Joel Pinter, J. David Pajerowski, Kyle R. Spinler, Jae Won Shin, Manorama Tewari, Florian Rehfeldt, David W. Speicher, Dennis E. Discher

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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.
    Original languageEnglish
    Article number1240104
    JournalScience
    Volume341
    Issue number6149
    DOIs
    Publication statusPublished - 2013

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