title: Stem cell depletion in Hutchinson-Gilford progeria syndrome.
abstract: 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.
authors: Department of Biosciences and Nutrition, Center for Biosciences, Karolinska Institutet, Karolinska University Hospital, Huddinge, Novum, Stockholm, Sweden.
authors: Ylva
authors: Y
authors: Rosengardten
authors: Tomás
authors: T
authors: McKenna
authors: Diana
authors: D
authors: Grochová
authors: Maria
authors: M
authors: Eriksson
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D019588:Aging, Premature / Q000235:genetics*; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D015870:Gene Expression; D007249:Inflammation / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology*; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D011371:Progeria / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
chemical_list: D034904:Lamin Type A; D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse