Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells.
Level 5 - mechanism / opinion, no new human data
In vitro bench and sequencing study on human cell lines
PubMed 22162363 · doi:10.1002/stem.1011
What was done
Researchers performed whole-exome sequencing on human foreskin fibroblasts and their derived induced pluripotent stem cells (iPSCs) at two different passages. They used ultradeep amplicon sequencing to determine whether mutations preexisted in the parental fibroblasts and ran simulations to estimate mutation intensity during reprogramming compared to standard culture background rates.
What was found
In vitro passaging accounted for 7% of the coding point mutation load in iPSCs, 19% of mutations preexisted as rare mutations in parental fibroblasts, and the remaining 74% were acquired during reprogramming. Simulation indicated that mutation intensity during reprogramming was ninefold higher than the background mutation rate in culture.
Why it matters
This study shows that the process of factor-induced reprogramming itself introduces the majority of coding mutations in human iPSCs, highlighting a key genomic stability and safety consideration for cell therapy applications.
Limits
The abstract does not disclose the sample size (number of fibroblast donor lines or iPSC clones analyzed). It is an in vitro genomic study without functional or tumorigenicity assays, relying partly on simulation for the mutation intensity estimate.
Cited by
- supports When somatic cells are reprogrammed into induced pluripotent stem cells, somatic DNA mutations are retained and persist.