DNA damage triggers reprogramming of differentiated cells into stem cells in Physcomitrella

Area of Science:

• Plant biology
• Molecular biology
• Cellular reprogramming

Background:

• DNA damage typically threatens genome integrity and cell viability.
• Cellular responses to DNA damage often involve cell cycle arrest or apoptosis.
• Understanding triggers for stem cell formation is crucial for developmental biology.

Purpose of the Study:

• To investigate if DNA damage can induce cellular reprogramming into stem cells.
• To identify the molecular mechanisms underlying DNA damage-induced cell reprogramming.
• To explore the role of specific kinases and factors in this process.

Main Methods:

• Induction of DNA strand breaks in *Physcomitrella patens* using zeocin.
• Monitoring activation of the STEM CELL-INDUCING FACTOR 1 (STEMIN1) promoter.
• Assessing cell division patterns and stem cell formation.
• Investigating the roles of ATR and ATM kinases using genetic approaches.

Main Results:

• Transient DNA strand breaks induced reprogramming of differentiated leaf cells into stem cells without cell death.
• Activated leaf cells formed chloronema apical stem cells capable of generating new gametophores.
• The DNA damage sensor ATR kinase and STEMIN1 were essential for this reprogramming.
• ATR kinase activity was indispensable for STEMIN1 induction by DNA strand breaks.

Conclusions:

• DNA strand breaks can act as a trigger for cellular reprogramming towards stem cells.
• The ATR kinase and STEMIN1 pathway mediates DNA damage-induced stem cell formation.
• This study reveals a novel function for DNA damage response in developmental plasticity.