Stem cell depletion in Hutchinson-Gilford progeria syndrome

Aging Cell. 2011 Dec;10(6):1011-20. doi: 10.1111/j.1474-9726.2011.00743.x. Epub 2011 Oct 11.


Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a very rare genetic disorder with clinical features suggestive of premature aging. Here, we show that induced expression of the most common HGPS mutation (LMNA c.1824C>T, p.G608G) results in a decreased epidermal population of adult stem cells and impaired wound healing in mice. Isolation and growth of primary keratinocytes from these mice demonstrated a reduced proliferative potential and ability to form colonies. Downregulation of the epidermal stem cell maintenance protein p63 with accompanying activation of DNA repair and premature senescence was the probable cause of this loss of adult stem cells. Additionally, upregulation of multiple genes in major inflammatory pathways indicated an activated inflammatory response. This response has also been associated with normal aging, emphasizing the importance of studying progeria to increase the understanding of the normal aging process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism
  • Aging, Premature / genetics*
  • Animals
  • Cell Count
  • Cell Differentiation / genetics*
  • Cell Proliferation
  • Disease Models, Animal
  • Epidermal Cells
  • Epidermis / metabolism
  • Gene Expression
  • Inflammation / complications
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Keratinocytes / metabolism
  • Keratinocytes / pathology*
  • Lamin Type A / genetics*
  • Lamin Type A / metabolism
  • Mice
  • Mutation
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Primary Cell Culture
  • Progeria / complications
  • Progeria / genetics*
  • Progeria / metabolism
  • Signal Transduction / genetics
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Wound Healing / genetics


  • Lamin Type A
  • Phosphoproteins
  • Trans-Activators
  • Trp63 protein, mouse