Genomics

Dataset Information

0

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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE26093 | GEO | 2010/12/23

SECONDARY ACCESSION(S): PRJNA135167

REPOSITORIES: GEO

Similar Datasets

| E-GEOD-26093 | biostudies-arrayexpress
2008-02-09 | GSE10123 | GEO
| E-GEOD-24487 | biostudies-arrayexpress
| E-GEOD-47553 | biostudies-arrayexpress
| E-GEOD-41757 | biostudies-arrayexpress
2011-03-14 | GSE24487 | GEO
2022-09-12 | GSE202368 | GEO
2022-09-12 | GSE202364 | GEO
2015-06-05 | GSE51202 | GEO
2015-06-05 | GSE51203 | GEO