Elucidating the Role of Human ZSCAN4 in the Maintenance of Induced Pluripotent Stem Cells

Abstract

Induced pluripotent stem cells (iPSCs) hold transformative promise for regenerative medicine, disease modelling, and drug discovery. However, the translational utility of iPSCs remains constrained by genomic instability and accumulating genetic abnormalities encountered during reprogramming and prolonged culture. While the zinc finger transcription factor ZSCAN4 has been established as a critical regulator of telomere elongation and chromosomal integrity in murine models, its functional role in human cellular reprogramming and maintenance has remained uncharacterized. This thesis addresses this critical gap through a dual-pronged approach combining protein engineering, non-integrative iPSC derivation, and CRISPR-Cas9-mediated gene knockout.