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Published on: July 17, 2019
Hes1 desynchronizes differentiation of pluripotent cells by modulating STAT3 activity
Xinzhi Zhou1, Andrew J H Smith, Anna Waterhouse
1MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Stem Cells (Dayton, Ohio)
|May 8, 2013
Summary
Pluripotent stem cells differentiate asynchronously due to variability in Hes1 gene expression. This gene delays cell differentiation, ensuring flexibility in early embryonic development and lineage allocation.
Area of Science:
- Developmental biology
- Stem cell biology
- Molecular genetics
Background:
- Early embryonic development requires flexible lineage allocation.
- Pluripotent stem cells exhibit asynchronous differentiation in vitro.
- Stochastic Hes1 expression influences lineage decisions.
Purpose of the Study:
- To investigate the role of Hes1 in asynchronous differentiation of pluripotent stem cells.
- To elucidate the mechanism by which Hes1 delays exit from the pluripotent state.
Main Methods:
- Clonal commitment assay to assess differentiation timing.
- Analysis of Hes1 gene expression variability.
- Investigating Hes1's effect on STAT3 responsiveness.
Main Results:
- Pluripotent cells commit to differentiation asynchronously under uniform conditions.
- Hes1 delays the exit from the pluripotent state into all lineages.
- Hes1 amplifies STAT3 responsiveness in a cell-autonomous manner.
Conclusions:
- Variability in Hes1 expression explains asynchronous STAT3 responsiveness in individual stem cells.
- Hes1's role in delaying differentiation contributes to flexibility in early embryonic development.
- Understanding Hes1 function is crucial for controlling stem cell differentiation and lineage allocation.
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