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Divergent reprogramming routes lead to alternative stem-cell states
Peter D Tonge1, Andrew J Corso2, Claudio Monetti1
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Nature
|December 16, 2014
Summary
Researchers discovered a new type of pluripotent cell beyond induced pluripotent stem cells (iPSCs). This alternative state arises from unique epigenetic changes during somatic cell reprogramming, expanding our understanding of cellular plasticity.
Area of Science:
- Cell Biology
- Developmental Biology
- Stem Cell Research
Background:
- Pluripotency enables cells to differentiate into all three embryonic germ layers.
- Pluripotent cells are derived from embryonic stem cells or through somatic cell reprogramming into induced pluripotent stem cells (iPSCs).
- Mouse iPSCs can generate complete iPSC-derived embryos and mice, representing a stringent test of pluripotency.
Purpose of the Study:
- To investigate alternative outcomes of somatic reprogramming beyond the established iPSC state.
- To characterize reprogrammed cells independently of predefined iPSC definitions.
- To explore the full spectrum of reprogrammed cellular phenotypes.
Main Methods:
- Somatic cell reprogramming of mouse embryonic fibroblasts.
- Maintenance of elevated reprogramming factor expression.
- Characterization of reprogrammed cell epigenetic modifications and pluripotency markers.
- Assessment of alternative pluripotent states.
Main Results:
- Elevated reprogramming factor expression led to unique epigenetic modifications in mouse embryonic fibroblasts.
- A stable, Nanog-positive, alternative pluripotent cell state was identified.
- This demonstrates that the pluripotent spectrum includes multiple distinct cell states.
Conclusions:
- The study proves that the pluripotent spectrum is broader than previously understood.
- Alternative pluripotent cell states can be generated through somatic reprogramming.
- This expands the definition and understanding of cellular pluripotency and reprogramming outcomes.
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