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Abstract：
Reprogramming human somatic cells into a pluripotent state, achieved through the activation of well-defined transcriptional factors known as OSKM factors, offers significant potential for regenerative medicine. While OSKM factors are a robust reprogramming method, efficiency remains a challenge, with only a fraction of cells undergoing successful reprogramming. To address this, we explored genes related to genomic integrity and cellular survival, focusing on iPSCs (A53T-PD1) that displayed enhanced colony stability. Our investigation had revealed three candidate genes CCN3, POSTN, and PTHLH that exhibited differential expression levels and potential roles in iPSC stability. Subsequent analyses identified various protein interactions for these candidate genes. POSTN, significantly upregulated in A53T-PD1 iPSC line, showed interactions with extracellular matrix components and potential involvement in Wnt signaling. CCN3, also highly upregulated, demonstrated interactions with TP53, CDKN1A, and factors related to apoptosis and proliferation. PTHLH, while upregulated, exhibited interactions with CDK2 and genes involved in cell cycle regulation. RT-qPCR validation confirmed elevated CCN3 and PTHLH expression in A53T-PD1 iPSCs, aligning with RNA-seq findings. These genes\' roles in preserving pluripotency and cellular stability require further exploration. In conclusion, we identified CCN3, POSTN, and PTHLH as potential contributors to genomic integrity and pluripotency maintenance in iPSCs. Their roles in DNA repair, apoptosis evasion, and signaling pathways could offer valuable insights for enhancing reprogramming efficiency and sustaining pluripotency. Further investigations are essential to unravel the mechanisms underlying their actions.
摘要：
将人类体细胞重新编程为多能状态，通过激活定义明确的转录因子OSKM因子来实现，为再生医学提供了巨大的潜力。虽然OSKM因子是一种稳健的重编程方法，效率仍然是一个挑战，只有一小部分细胞经历成功的重编程。为了解决这个问题，我们探索了与基因组完整性和细胞存活相关的基因，集中于显示增强的集落稳定性的iPSC（A53T-PD1）。我们的调查揭示了三个候选基因CCN3，POSTN，和PTHLH表现出差异表达水平和在iPSC稳定性中的潜在作用。随后的分析鉴定了这些候选基因的各种蛋白质相互作用。POSTN,在A53T-PD1iPSC细胞系中显著上调，显示与细胞外基质成分的相互作用，并可能参与Wnt信号传导。CCN3，也高度上调，显示与TP53、CDKN1A、以及与细胞凋亡和增殖有关的因素。PTHLH,虽然上调，表现出与CDK2和细胞周期调控相关基因的相互作用。RT-qPCR验证证实A53T-PD1iPSC中CCN3和PTHLH表达升高，与RNA-seq结果比对。这些基因在保持多能性和细胞稳定性方面的作用需要进一步探索。总之,我们确定了CCN3，POSTN，和PTHLH是iPSC基因组完整性和多能性维持的潜在贡献者。它们在DNA修复中的作用，凋亡逃避，和信号通路可以为提高重编程效率和维持多能性提供有价值的见解。进一步的调查对于解开其行动背后的机制至关重要。
