Dataset Information


A human iPSC model of Hutchinson Gilford Progeria Syndrome reveals a possible mesenchymal stem cell defect

ABSTRACT: Hutchinson Gilford Progeria Syndrome (HGPS) is a rare, sporadic genetic disease caused by mutations in the nuclear lamin A gene. In most cases the mutation creates an efficient donor-splice site that generates an altered transcript encoding a truncated lamin A protein, progerin. In vitro studies have indicated that progerin can disrupt nuclear function. HGPS affects mainly mesenchymal lineages but the shortage of patient material has precluded a tissue-wide molecular survey of progerin’s cellular impact. We report here a new, induced pluripotent stem cell (iPSC)-based model for studying HGPS. HGPS dermal fibroblasts were reprogrammed into iPSC lines using a cocktail of the transcription factor genes, OCT4, SOX2, KLF4 and C-MYC. The iPSC cells were differentiated into neural progenitors (NPs), endothelial cells (ECs), fibroblast-like cells and mesenchymal stem cells (MSCs). Progerin levels in the different cell types followed the pattern MSC≥ fibroblast>EC>>NP. Functionally, we detected a major impact of progerin on MSC function. We show that HGPS-MSCs are vulnerable to the ischemic conditions found in a murine hind limb recovery model and an in vitro hypoxia assay, as well as showing enhanced sensitivity in a serum starvation assay. Since there is widespread consensus that MSCs reside in low oxygen niches in vivo, we propose that these conditions lead to an accelerated depletion of the MSC pool in HGPS patients with consequent accretion of mesenchymal tissue. Analysis of iPSCs, hESCs and parental fibroblasts at the gene expression level. The comparison analysis in the present study was expected to show the similarity between iPSCs, hESCs and parental fibroblasts. Results provide important information of the differences between iPSCs, hESCs and parental fibroblasts. Total RNA was obtained from different samples (iPSCs, hESCs, and fibroblasts) separately.

ORGANISM(S): Homo sapiens  

SUBMITTER: Colin Stewart   Alan Colman  Jinqiu Zhang  Qizhou Lian  Guili Zhu  Rafidah A Mutalif  Hung-Fat Tse  FAN ZHOU  Fan Zhou  Cindy Tan  Raju Navasankari  Lin Sui  Yuelin Zhang 

PROVIDER: E-GEOD-26093 | ArrayExpress | 2010-12-23



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A human iPSC model of Hutchinson Gilford Progeria reveals vascular smooth muscle and mesenchymal stem cell defects.

Zhang Jinqiu J   Lian Qizhou Q   Zhu Guili G   Zhou Fan F   Sui Lin L   Tan Cindy C   Mutalif Rafidah Abdul RA   Navasankari Raju R   Zhang Yuelin Y   Tse Hung-Fat HF   Stewart Colin L CL   Colman Alan A  

Cell stem cell 20101223 1

The 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, an  ...[more]

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