Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
Level 5 - mechanism / opinion, no new human data
Basic science bench research and animal model experiments.
PubMed 16904174 · doi:10.1016/j.cell.2006.07.024
What was done
Researchers introduced four defined transcription factors (Oct3/4, Sox2, c-Myc, and Klf4) into mouse embryonic and adult fibroblast cultures under embryonic stem (ES) cell culture conditions. The resulting induced pluripotent stem (iPS) cells were evaluated for ES cell-like morphology, growth properties, marker gene expression, teratoma formation across all three germ layers following subcutaneous injection into nude mice, and developmental potential via blastocyst injection.
What was found
The abstract reports no numerical figures or rates. The introduction of the four factors generated iPS cells from both embryonic and adult fibroblasts, and Nanog was found to be dispensable. The generated iPS cells exhibited ES cell morphology, growth properties, and marker expression, produced multi-lineage tumors containing tissues from all three germ layers in nude mice, and contributed to embryonic development after blastocyst injection.
Why it matters
This work demonstrated that terminal cellular differentiation can be reversed to pluripotency through the expression of a small set of defined transcription factors without requiring nuclear transfer or cell fusion.
Limits
The abstract reports no quantitative data regarding reprogramming efficiency, transformation kinetics, or success rates. The work was restricted to mouse cells and animal models, and did not evaluate human cellular reprogramming, insertional mutagenesis risks, or oncogenic potential related to c-Myc expression.
Cited by
- supports Shinya Yamanaka demonstrated that introducing specific transcription factors (Yamanaka factors) into somatic cells such as fibroblasts can revert them into induced pluripotent stem cells.