کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2077543 1079725 2011 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A Human iPSC Model of Hutchinson Gilford Progeria Reveals Vascular Smooth Muscle and Mesenchymal Stem Cell Defects
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
A Human iPSC Model of Hutchinson Gilford Progeria Reveals Vascular Smooth Muscle and Mesenchymal Stem Cell Defects
چکیده انگلیسی

SummaryThe segmental premature aging disease Hutchinson-Gilford Progeria syndrome (HGPS) is caused by a truncated and farnesylated form of Lamin A called progerin. HGPS affects mesenchymal lineages, including the skeletal system, dermis, and vascular smooth muscle (VSMC). To understand the underlying molecular pathology of HGPS, we derived induced pluripotent stem cells (iPSCs) from HGPS dermal fibroblasts. The iPSCs were differentiated into neural progenitors, endothelial cells, fibroblasts, VSMCs, and mesenchymal stem cells (MSCs). Progerin levels were highest in MSCs, VSMCs, and fibroblasts, in that order, with these lineages displaying increased DNA damage, nuclear abnormalities, and HGPS-VSMC accumulating numerous calponin-staining inclusion bodies. Both HGPS-MSC and -VSMC viability was compromised by stress and hypoxia in vitro and in vivo (MSC). Because MSCs reside in low oxygen niches in vivo, we propose that, in HGPS, this causes additional depletion of the MSC pool responsible for replacing differentiated cells lost to progerin toxicity.


► Five different cell lineages are made from human progeria (HGPS) iPSCs
► Progerin expression is highest in MSCs, VMSCs and fibroblasts
► HGPS-MSC survival is impaired by hypoxia in vitro and in vivo
► HGPS-VSMCs, also stress sensitive, accumulate calponin-staining inclusion bodies

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 8, Issue 1, 7 January 2011, Pages 31–45
نویسندگان
, , , , , , , , , , , ,