SenSet defines cell-type specific senescence signatures in the aged human lung

Area of Science:

• Cellular and Molecular Biology
• Aging Research
• Bioinformatics

Background:

• Cellular senescence is an irreversible cell cycle arrest linked to aging and disease.
• Senescence is heterogeneous and challenging to study in vivo due to low cell abundance, especially in the human lung.
• Existing methods struggle to comprehensively identify senescent cells in complex tissues.

Purpose of the Study:

• To develop a robust method for identifying senescent cells in the human lung.
• To create a comprehensive gene marker set for lung senescence (SenSet).
• To analyze cell-type-specific senescence signatures in aging and environmentally exposed lungs.

Main Methods:

• Utilized a positive-unlabeled learning framework on the Human Lung Cell Atlas (HLCA) dataset.
• Generated and validated the SenSet gene list.
• Employed ex vivo human 3D lung tissue culture models with senescence inducers (bleomycin, doxorubicin, irradiation) for validation.

Main Results:

• Developed SenSet, a comprehensive list of senescence marker genes for human lungs.
• Validated SenSet's sensitivity and accuracy in characterizing senescence.
• Identified distinct, cell-type-specific senescence signatures in lung populations associated with aging and environmental factors.

Conclusions:

• SenSet provides a powerful tool for studying lung senescence.
• This research offers fundamental insights into the role of senescent cells in the healthy aging lung.
• Findings have significant implications for understanding and potentially treating lung diseases like cancer, fibrosis, COPD, and asthma.