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Beyond selection: How chromosome 12 gain dominates stem cell genomes.

Orléna Benamozig1, Ofer Shoshani1

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Trisomy 12 in human-induced pluripotent stem cells (iPSCs) arises from chromosome missegregation due to telomere erosion. This genetic instability, combined with a growth advantage, leads to rapid iPSC population expansion.

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Area of Science:

  • Cell Biology
  • Genetics
  • Stem Cell Research

Background:

  • Trisomy 12 is a common observation in pluripotent stem cell lines.
  • The underlying mechanisms driving trisomy 12 in induced pluripotent stem cells (iPSCs) remain incompletely understood.

Purpose of the Study:

  • To investigate the driving forces behind trisomy 12 in human iPSCs.
  • To elucidate the relationship between sub-telomeric erosion, chromosome missegregation, and population dynamics in iPSCs.

Main Methods:

  • Analysis of human-induced pluripotent stem cells exhibiting trisomy 12.
  • Investigation of chromosomal missegregation events.
  • Assessment of sub-telomeric integrity and its correlation with trisomy.

Main Results:

  • Trisomy 12 in iPSCs is driven by continuous chromosome missegregation events.
  • Sub-telomeric erosion is identified as a key factor contributing to missegregation.
  • A modest growth advantage associated with trisomy 12 facilitates rapid population takeover.

Conclusions:

  • Sub-telomeric erosion and subsequent missegregation are the primary drivers of trisomy 12 in iPSCs.
  • The genetic instability coupled with a growth advantage explains the prevalence of trisomy 12 in iPSC cultures.
  • Understanding these mechanisms is crucial for stem cell research and therapeutic applications.