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Updated: May 26, 2026
11:38
RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
Published on: November 26, 2018
Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells.
Junfeng Ji1, Siemon H Ng, Vivek Sharma
1Cancer Genomics, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
Stem Cells (Dayton, Ohio)
|December 14, 2011
Summary
Cellular reprogramming stress significantly increases mutation rates in induced pluripotent stem cells (iPSCs). Most mutations arise during reprogramming, not culture, highlighting risks for clinical applications.
Area of Science:
- Stem Cell Biology
- Genetics
- Genomics
Background:
- Mutations in human induced pluripotent stem cells (iPSCs) can compromise their clinical utility.
- The origins of these mutations, particularly concerning reprogramming-induced stress, remain unclear.
Purpose of the Study:
- To investigate whether stress from oncogene expression during reprogramming contributes to the mutation load in iPSCs.
Main Methods:
- Whole exome sequencing of human foreskin fibroblasts and their derived iPSCs.
- Ultradeep amplicon sequencing to identify pre-existing and newly acquired mutations.
Main Results:
- In vitro passaging accounted for 7% of the mutation load in iPSCs.
- 19% of mutations were pre-existing rare variants in parental fibroblasts.
- Approximately 74% of mutations were acquired during the cellular reprogramming process.
- Reprogramming mutation intensity was ninefold higher than the background rate.
Conclusions:
- Cellular reprogramming stress is a significant factor contributing to the mutation load in iPSCs.
- The findings underscore the need to mitigate reprogramming-induced mutations for safe clinical use of iPSCs.
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