Mechanical control of DNA methylation in regenerative cells

Mesenchymal stromal cells (MSC) exposed to stiff environment lose regeneration potential and acquire a scar-producing myofibroblast (MF) phenotype. We published that 4-weeks culture on soft-tissue-like surfaces not only prevents acute MF features but imprints memory that protects MSC from subsequent mechanical MF activation. Epigenetic methylation of DNA by methyltransferases (DNMTs) memorizes MF phenotype in disease. We hypothesize that mechanical environment controls MF memory by DNA methylation in MSC. We will subject MSC to various mechanical stress conditions in culture and test the effect on global DNA methylation, DNMT expression. Our data will establish mechanical factors as regulators of epigenetic memory in MSC. We will reveal how mechanics regulate DNA methylation to design therapeutic MSC with epigenetically stabilized regeneration potential and suppressed MF activation. Ultimately, we aim to improve the health of Canadians who are impacted by scarring of large area burn wounds.

Faculty Supervisor:

Boris Hinz

Student:

Partner:

Reutlingen University

Discipline:

Life Sciences

Sector:

Education

University:

University of Toronto

Program: