Revealing genetic mutations affecting the safety of induced pluripotent stem cells

A groundbreaking study published in *Nature Communications* has unveiled new insights into the safety of induced pluripotent stem cells (iPS cells), thanks to a collaborative effort between Professor Tian Jianhui from China Agricultural University, Professor Gao Shaorong from Tongji University, and researcher Cai Jun from the Chinese Academy of Sciences. The research revealed that genetic mutations occurring during the reprogramming process can significantly reduce the developmental potential of iPS cells, offering crucial guidance for future safety assessments. Animal cloning has long been a key method in somatic cell reprogramming. Since the famous cloned sheep Dolly was born in 1996, this field has gained significant attention in animal science. In 2006, Japanese scientist Shinya Yamanaka introduced a revolutionary technique using viral vectors to deliver four key transcription factors into adult cells, transforming them into iPS cells—resembling embryonic stem cells. This discovery earned him the 2012 Nobel Prize in Physiology or Medicine, as it opened new possibilities for regenerative medicine and the preservation of genetic resources. However, concerns remain about whether these iPS cells carry genetic mutations and how they might affect their functionality and safety. A recent study by Professor Tian’s team found that the methylation level of the imprinted gene Zrsr1 influences the quality of iPS cells. Building on this, the team, in collaboration with Professor Gao, successfully generated iPS mice over six consecutive generations, creating a valuable model for studying mutations and evaluating iPS cell safety during reprogramming. The results showed that after repeated induction, the viability of the mice gradually declined, leading to death. Further analysis revealed that the reprogramming process led to numerous single nucleotide variations (SNVs) and that some of these mutations were passed into the germ line. This study is the first to demonstrate that SNVs induced during reprogramming pose real safety risks, providing a solid foundation for assessing the safety of iPS cells in future applications. This important work was co-authored by Professor Tian Jianhui from China Agricultural University, Professor Gao Shaorong from Tongji University, and Dr. Cai Jun from the Chinese Academy of Sciences. The lead authors include Dr. Gao Shuai from China Agricultural University, Dr. Zheng Caihong from the Institute of Genomics, and Dr. Changgang. The findings highlight the importance of understanding and mitigating genetic risks in iPS cell technology, paving the way for safer and more effective stem cell-based therapies.

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