PML2-mediated thread-like nuclear bodies mark late senescence in Hutchinson-Gilford progeria syndrome

Aging Cell. 2020 Jun;19(6):e13147. doi: 10.1111/acel.13147. Epub 2020 Apr 29.


Progerin accumulation disrupts nuclear lamina integrity and causes nuclear structure abnormalities, leading to premature aging, that is, Hutchinson-Gilford progeria syndrome (HGPS). The roles of nuclear subcompartments, such as PML nuclear bodies (PML NBs), in HGPS pathogenesis, are unclear. Here, we show that classical dot-like PML NBs are reorganized into thread-like structures in HGPS patient fibroblasts and their presence is associated with late stage of senescence. By co-immunoprecipitation analysis, we show that farnesylated Progerin interacts with human PML2, which accounts for the formation of thread-like PML NBs. Specifically, human PML2 but not PML1 overexpression in HGPS cells promotes PML thread development and accelerates senescence. Further immunofluorescence microscopy, immuno-TRAP, and deep sequencing data suggest that these irregular PML NBs might promote senescence by perturbing NB-associated DNA repair and gene expression in HGPS cells. These data identify irregular structures of PML NBs in senescent HGPS cells and support that the thread-like PML NBs might be a novel, morphological, and functional biomarker of late senescence.

Keywords: HGPS; PML2; senescence; thread-like PML NBs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line
  • Cell Nucleus / metabolism
  • Cellular Senescence / physiology
  • Female
  • Fibroblasts
  • Humans
  • Lamin Type A / metabolism*
  • Progeria / genetics
  • Progeria / metabolism*
  • Progeria / pathology*
  • Transfection
  • Young Adult


  • Lamin Type A