Generation of inducible LMNA and Progerin hiPSC lines for controlled modelling of cellular ageing.

Modelling human ageing in vitro remains challenging due to the limited ability of hiPSC systems to recapitulate progressive cellular decline. We generated hiPSC lines with a dual-cassette doxycycline-inducible system enabling controlled Progerin expression as a model of accelerated ageing, alongside matched inducible LMNA and GFP control lines. TALEN-mediated genome editing generated a Tet-On system comprising a constitutive M2rtTA regulatory cassette and TRE-driven transgene cassette targeted to the AAVS1 locus. Targeted integration was confirmed by PCR and sequencing confirmed the Progerin-specific deletion. The engineered lines retained pluripotency and demonstrated strong inducible expression, providing a versatile platform for modelling ageing-associated cellular phenotypes.