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Generation of inducible LMNA and Progerin hiPSC lines for controlled modelling of cellular ageing
Desi Veleva1, Cesar L Moreno1, Micah Clarke2
1Australian Institute for Bioengineering & Nanotechnology (AIBN), The University of Queensland, St. Lucia, Brisbane, Australia.
Abstract:
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.
