Open AccessStem cell depletion in Hutchinson–Gilford progeria syndrome
Author(s) -
Rosengardten Ylva,
McKenna Tomás,
Grochová Diana,
Eriksson Maria
Publication year - 2011
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2011.00743.x
Subject(s) - progeria , lmna , premature aging , biology , senescence , downregulation and upregulation , stem cell , microbiology and biotechnology , werner syndrome , dna repair , cancer research , mutation , genetics , immunology , gene , helicase , rna
Summary 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.