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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1391 Scopus citations

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 languageAmerican English
Article number1240104
JournalScience
Volume341
Issue number6149
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Dive into the research topics of 'Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation'. Together they form a unique fingerprint.

Cite this