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Published on: January 8, 2017

TAp63 prevents premature aging by promoting adult stem cell maintenance

Xiaohua Su1, Maryline Paris, Young Jin Gi

  • 1Department of Molecular and Cellular Oncology, Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Cell Stem Cell
|July 3, 2009
PubMed

Insights

The protein TAp63 is crucial for maintaining adult skin stem cells. Its absence leads to premature skin aging and cellular senescence in epidermal and dermal precursors.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Dermatology

Background:

  • Cellular mechanisms governing adult tissue stem cell maintenance remain largely elusive.
  • Understanding these mechanisms is critical for addressing age-related tissue degeneration.

Purpose of the Study:

  • To investigate the role of the p53 family member TAp63 in the maintenance of adult skin stem cells.
  • To determine the consequences of TAp63 loss on epidermal and dermal precursor cells and skin aging.

Main Methods:

  • Development and utilization of a TAp63 conditional knockout mouse model.
  • Genetic ablation of TAp63 in the germline (TAp63(-/-)) and in K14-expressing epidermal basal cells (TAp63(fl/fl);K14cre+).
  • Phenotypic analysis of skin aging, cellular senescence, proliferation, and genomic stability.

Main Results:

  • TAp63(-/-) mice exhibited premature aging phenotypes, including skin blistering, ulcerations, and decreased hair morphogenesis.
  • Dermal and epidermal precursors lacking TAp63 displayed defective proliferation, premature senescence, and genomic instability.
  • These cellular defects in precursors correlated with the observed premature aging phenotypes.

Conclusions:

  • TAp63 is essential for maintaining adult skin stem cell populations.
  • TAp63 regulates cellular senescence and genomic stability in skin precursors, thereby preventing premature skin aging.
  • Loss of TAp63 function accelerates the aging process of the skin.

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