Press Release

Dynamic stem cell selection safeguards the genomic integrity of the epidermis

Published: January 26, 2022


• A fate-tracing method for EpiSCs with DNA double-strand breaks (DSBs) was developed

• EpiSCs with DSBs promptly differentiate to be selectively eliminated from the niche

• DSB-induced differentiation is mediated by p53-Notch signaling with the loss of ITGB1

• The stem cell elimination is coupled with augmented clonal expansion of intact EpiSCs


Maintaining genomic integrity and stability is crucial for life; yet, no tissue-driven mechanism that robustly safeguards the epithelial genome has been discovered. Epidermal stem cells (EpiSCs) continuously replenish the stratified layers of keratinocytes that protect organisms against various environmental stresses. To study the dynamics of DNA-damaged cells in tissues, we devised an in vivo fate tracing system for EpiSCs with DNA double-strand breaks (DSBs) and demonstrated that those cells exit from their niches. The clearance of EpiSCs with DSBs is caused by selective differentiation and delamination through the DNA damage response (DDR)-p53-Notch/p21 axis, with the downregulation of ITGB1. Moreover, concomitant enhancement of symmetric cell divisions of surrounding stem cells indicates that the selective elimination of cells with DSBs is coupled with the augmented clonal expansion of intact stem cells. These data collectively demonstrate that tissue autonomy through the dynamic coupling of cell-autonomous and non-cell-autonomous mechanisms coordinately maintains the genomic quality of the epidermis.

Journal Article

JOURNAL Developmental Cell

TITLE:Dynamic stem cell selection safeguards the genomic integrity of the epidermi


Correspondence to

 Emi K. Nishimura, MD, PhD,Professor

Department of Stem Cell Biology,
Medical Research Institute,
Tokyo Medical and Dental University (TMDU)

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