Deciphering the Dynamic Molecular Program of Radiation-Induced Endothelial Senescence

Area of Science:

• Cell Biology
• Radiation Oncology
• Systems Biology

Background:

• Cellular senescence, induced by radiation, has dual roles in tumor suppression and normal tissue injury.
• Endothelial cells (ECs) are implicated in radiation-induced normal tissue damage.
• The precise impact of radiation on EC senescence is complex due to dose, fractionation, and the dynamic, heterogeneous nature of senescence.

Purpose of the Study:

• To investigate the dynamic transcriptional program of radiation-induced senescence in endothelial cells using a systems biology approach.
• To understand the heterogeneous senescent status of irradiated ECs and the underlying molecular mechanisms.

Main Methods:

• In vitro systems biology approach.
• Flow cytometry and single-cell RNA sequencing.
• Deciphering the senescence-associated transcriptional program.

Main Results:

• Irradiated ECs exhibit a heterogeneous senescent status.
• The Interleukin-1 signaling pathway is identified as a key regulator of radiation-induced premature EC senescence.
• Endothelial-to-mesenchymal transition shares significant hallmarks with radiation-induced senescence.

Conclusions:

• This study elucidates the dynamics of radiation-induced premature senescence in ECs.
• It highlights the influence of radiation dose on senescence and identifies key molecular pathways involved.
• The findings contribute to understanding the heterogeneous senescent phenotype of ECs post-irradiation.