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Related Experiment Video

Updated: Jan 6, 2026

Efficient Sampling of Genetically Encoded Biosensor Design Space Enabled with a Design of Experiments and Automation Workflow
08:58

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Published on: October 17, 2025

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Copy number variation and selection during reprogramming to pluripotency.

Samer M Hussein1, Nizar N Batada, Sanna Vuoristo

  • 1Samuel Lunenfeld Research Institute, Toronto, Ontario M5T 3H7, Canada.

Nature
|March 4, 2011
PubMed
Summary
This summary is machine-generated.

Induced pluripotent stem (iPS) cell reprogramming generates copy number variations (CNVs) in early passages, compromising genomic integrity. However, cell culture rapidly selects against these genetic changes, improving iPS cell quality over time.

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Area of Science:

  • Stem cell biology
  • Genomics
  • Epigenetics

Background:

  • The low efficiency of reprogramming somatic cells into induced pluripotent stem (iPS) cells remains a significant challenge.
  • Understanding the factors influencing reprogramming efficiency, particularly genomic integrity, is crucial for advancing regenerative medicine.

Purpose of the Study:

  • To investigate whether the reprogramming process itself leads to genomic instability.
  • To characterize the nature and impact of genetic alterations during iPS cell generation and culture.

Main Methods:

  • Utilized high-resolution single nucleotide polymorphism (SNP) arrays to analyze copy number variations (CNVs).
  • Compared CNVs in human iPS cells at various passages with their original fibroblast cells and human embryonic stem (ES) cells.

Main Results:

  • Early-passage human iPS cells exhibited significantly more CNVs compared to intermediate-passage iPS cells, fibroblasts, and human ES cells.
  • Most CNVs arose de novo, creating genetic mosaicism in early-passage iPS cells, with many conferring a selective disadvantage.
  • In vitro expansion of human iPS cells rapidly selected against cells with CNVs.

Conclusions:

  • The reprogramming process can induce genomic instability, evidenced by de novo CNVs in early-passage iPS cells.
  • Cell culture and expansion exert selective pressure, favoring genetically stable cells and improving the quality of iPS cell lines over time.
  • These findings provide critical insights into the mechanisms affecting iPS cell efficiency and genomic integrity.