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Establishing a High Throughput Epidermal Spheroid Culture System to Model Keratinocyte Stem Cell Plasticity
Published on: January 30, 2021
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DeltaNp63 is essential for epidermal commitment of embryonic stem cells
Alain Medawar1, Thierry Virolle, Philippe Rostagno
1INSERM, U898, Nice, France.
Plos One
|October 18, 2008
Summary
The study reveals that the DeltaNp63 isoform is crucial for epidermal development, specifically guiding embryonic stem cells towards stratified squamous epithelium. Loss of DeltaNp63 prevents this critical commitment pathway.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Epithelial Biology
Background:
- p63 is known to have complex roles in squamous epithelial development.
- The specific isoform and function of p63 in this process remain debated.
Purpose of the Study:
- To investigate the role of p63, specifically the DeltaNp63 isoform, in epithelial differentiation.
- To utilize an in vitro embryonic stem (ES) cell model mimicking early epidermal development.
Main Methods:
- Treatment of differentiating ES cells with Bone Morphogenetic Protein-4 (BMP-4).
- Analysis of DeltaNp63 gene expression during epithelial development.
- Investigating p63 loss-of-function and gain-of-function effects on cell fate commitment.
Main Results:
- DeltaNp63 isoform is activated by BMP-4, initiating ectodermal commitment.
- High DeltaNp63 expression is maintained throughout epithelial development.
- Loss of p63 function inhibits commitment to K5/K14-positive stratified epithelia.
- DeltaNp63 gain-of-function promotes commitment to K5/K14-positive epithelia.
- Other epithelial cell fates (K5/K18-positive) are not affected by DeltaNp63 manipulation.
Conclusions:
- DeltaNp63 is essential for the commitment of ES cells to the K5/K14-positive stratified squamous epithelial lineage.
- DeltaNp63 is dispensable for certain other types of epithelial differentiation.
