Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation.
Science
; 341(6149): 1240104, 2013 Aug 30.
Article
in En
| MEDLINE
| ID: mdl-23990565
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteogenesis
/
Stress, Mechanical
/
Cell Differentiation
/
Lamin Type A
/
Elasticity
/
Mesenchymal Stem Cells
Limits:
Animals
/
Humans
Language:
En
Journal:
Science
Year:
2013
Document type:
Article
Affiliation country:
Estados Unidos