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Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency
Published on: June 10, 2018
Natural and artificial routes to pluripotency
Winfried H Krueger1, Lindsey C Swanson, Borko Tanasijevic
1Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut 06269, USA.
The International Journal of Developmental Biology
|March 16, 2011
Summary
Naturally pluripotent cells have poised epigenetic states essential for differentiation. Artificial reprogramming methods create similar cells, but via different epigenetic routes, necessitating careful fidelity assessment.
Area of Science:
- Epigenetics
- Developmental Biology
- Stem Cell Biology
Background:
- Pluripotent cells (inner cell mass and embryonic stem cells) possess dynamic, uncondensed chromatin poised for differentiation.
- These cells exhibit specific histone modifications (bivalent domains) and express numerous genes at low levels.
- X chromosome inactivation is absent in female pluripotent cells, contributing to their developmental potential.
Purpose of the Study:
- To compare and contrast the epigenetic routes to pluripotency in natural and artificial reprogramming.
- To discuss the metastable nature of the pluripotent epigenome.
- To examine epigenetic factors influencing reprogramming fidelity.
Main Methods:
- Comparative analysis of epigenetic features in naturally pluripotent cells (ICM, ES cells) and artificially reprogrammed cells (SCNT, FMR, iPS).
- Review of histone modification patterns, chromatin dynamics, and gene expression profiles.
- Discussion of reprogramming pathways and potential epigenetic inaccuracies.
Main Results:
- Artificial reprogramming recapitulates many epigenetic features of natural pluripotency but follows distinct pathways.
- The pluripotent epigenome is inherently metastable.
- Incomplete or inaccurate reprogramming can arise from epigenetic deviations.
Conclusions:
- Understanding epigenetic similarities between embryonic and induced pluripotent stem cells is crucial for their therapeutic applications.
- The fidelity of artificial reprogramming is paramount for developing reliable cell-based therapies and disease models.
- Epigenetic assessment is critical for validating artificially reprogrammed cells.
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