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Series GSE26093 Query DataSets for GSE26093
Status Public on Dec 23, 2010
Title A human iPSC model of Hutchinson Gilford Progeria Syndrome reveals a possible mesenchymal stem cell defect
Organism Homo sapiens
Experiment type Expression profiling by array
Summary 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.
 
Overall design 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.
 
Contributor(s) Zhang J, Lian Q, Zhu G, Zhou F, Sui L, Tan C, Mutalif RA, Navasankari R, Zhang Y, Tse H, Stewart C, Colman A
Citation(s) 21185252
Submission date Dec 15, 2010
Last update date Mar 20, 2017
Contact name FAN ZHOU
E-mail(s) zhou.fan@imb.a-star.edu.sg
Phone +65-64070217
Fax +65-64072048
Organization name Institute of Medical Biolog
Lab STEM CELL DISEASE MODEL
Street address 8A Biomedical Grove
City Singapore
ZIP/Postal code 138648
Country Singapore
 
Platforms (1)
GPL6883 Illumina HumanRef-8 v3.0 expression beadchip
Samples (23)
GSM640588 N1-iPSC-1
GSM640589 N1-iPSC-2
GSM640590 PG1-iPSC-1
Relations
BioProject PRJNA135167

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE26093_RAW.tar 3.9 Mb (http)(custom) TAR
GSE26093_non-normalized.txt.gz 2.1 Mb (ftp)(http) TXT
Processed data included within Sample table

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