Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells.

Area of Science:

• Stem cell biology
• Epigenetics
• Genetics

Background:

• Induced pluripotent stem cells (iPSCs) offer therapeutic potential but can exhibit karyotypic abnormalities.
• Chromosomal aberrations in early-passage iPSCs raise safety concerns.
• The underlying mechanisms of chromosomal abnormalities in iPSCs remain unclear.

Purpose of the Study:

• To investigate the potential mutagenicity of the cell reprogramming process.
• To identify mechanisms contributing to chromosomal aberrations in early-passage iPSCs.
• To evaluate the efficacy of antioxidants in mitigating reprogramming-induced genetic instability.

Main Methods:

• Human dermal fibroblasts (HDFs) were reprogrammed using KMOS proteins and mRNAs.
• Clonal reprogramming and subculturing were employed to assess karyotypic stability.
• The antioxidant N-acetyl-cysteine (NAC) was administered during early reprogramming stages.

Main Results:

• Chromosomal aberrations were observed in a subset of newly generated iPSC clones.
• Clonal reprogramming excluded the inheritance of abnormalities from parental cells.
• NAC significantly reduced the incidence of chromosomal aberrations during early reprogramming.
• Established iPSC lines demonstrated restored karyotypic stability upon further culturing.

Conclusions:

• The reprogramming process itself can induce 'chromosomal mutagenicity'.
• Antioxidant intervention shows promise in preventing early-stage genetic instability during iPSC generation.
• Further research is warranted to fully elucidate and mitigate reprogramming-associated genetic risks.