Abstract: Reprogramming human somatic cells into induced pluripotent stem cells (iPSCs) using the well-known OSKM transcription factors holds promise for regenerative medicine. However, the efficiency of this process remains low, with only a small proportion of cells undergoing successful reprogramming. Disease-related mutations are one the considerable factors that affect reprogramming efficacy. Here, we employed RNA-seq to identify five transcription factors (GBX2, NANOGP8, SP8, PEG3, and ZIC1) that significantly increased iPSC colony formation from Parkinson’s disease samples. Additionally, we identified three candidate genes (CCN3, POSTN, and PTHLH) associated with enhanced colony stability and genomic integrity in iPSCs. Bioinformatics analyses indicated that GBX2, NANOGP8, SP8, PEG3, and ZIC1 play crucial roles in pluripotency and self-renewal, interacting with key regulators like OCT4, SOX2, NANOG, and KLF4. CCN3, POSTN, and PTHLH were found to contribute to iPSC stability through interactions with components of the extracellular matrix, Wnt signaling, and factors related to apoptosis and cell cycle regulation. RT-qPCR validation confirmed these findings. Our results underscore the potential of these transcription factors and candidate genes to improve reprogramming efficiency and preserve genomic integrity, prompting further exploration of their underlying mechanisms.
