Nuclear morphometrics coupled with machine learning identifies dynamic states of senescence across age.

Journal: Nature communications
Published Date:

Abstract

Cellular senescence is an irreversible state of cell cycle arrest with a complex role in tissue repair, aging, and disease. However, inconsistencies in identifying cellular senescence have led to varying conclusions about their functional significance. We developed a machine learning-based approach that uses nuclear morphometrics to identify senescent cells at single-cell resolution. By applying unsupervised clustering and dimensional reduction techniques, we built a robust pipeline that distinguishes senescent cells in cultured systems, freshly isolated cell populations, and tissue sections. Here we show that this method reveals dynamic, age-associated patterns of senescence in regenerating skeletal muscle and osteoarthritic articular cartilage. Our approach offers a broadly applicable strategy to map and quantify senescent cell states in diverse biological contexts, providing a means to readily assess how this cell fate contributes to tissue remodeling and degeneration across lifespan.

Authors

  • Sahil A Mapkar
    Musculoskeletal Research Center, Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY, USA.
  • Sarah A Bliss
    Musculoskeletal Research Center, Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY, USA.
  • Edgar E Perez Carbajal
    Musculoskeletal Research Center, Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY, USA.
  • Sean H Murray
    Musculoskeletal Research Center, Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY, USA.
  • Zhiru Li
    Musculoskeletal Research Center, Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY, USA.
  • Anna K Wilson
    Musculoskeletal Research Center, Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY, USA.
  • Vikrant Piprode
    Musculoskeletal Research Center, Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY, USA.
  • You Jin Lee
    Musculoskeletal Research Center, Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY, USA.
  • Thorsten Kirsch
    Musculoskeletal Research Center, Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY, USA.
  • Katerina S Petroff
    Musculoskeletal Research Center, Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY, USA.
  • Fengyuan Liu
    Bendable Electronics and Sensing Technologies (BEST) Group, James Watt School of Engineering, University of Glasgow, G12 8QQ Glasgow, UK.
  • Michael N Wosczyna
    Musculoskeletal Research Center, Department of Orthopedic Surgery, New York University Grossman School of Medicine, New York, NY, USA. michael.wosczyna@nyulangone.org.