Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-04

AUTHORS

Paola Scaffidi, Tom Misteli

ABSTRACT

The premature-ageing disease Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A. Progerin is also expressed sporadically in wild-type cells and has been linked to physiological ageing. Cells from HGPS patients exhibit extensive nuclear defects, including abnormal chromatin structure and increased DNA damage. At the organismal level, HGPS affects several tissues, particularly those of mesenchymal origin. How the cellular defects of HGPS cells lead to the organismal defects has been unclear. Here, we provide evidence that progerin interferes with the function of human mesenchymal stem cells (hMSCs). We find that expression of progerin activates major downstream effectors of the Notch signalling pathway. Induction of progerin in hMSCs changes their molecular identity and differentiation potential. Our results support a model in which accelerated ageing in HGPS patients, and possibly also physiological ageing, is the result of adult stem cell dysfunction and progressive deterioration of tissue functions. More... »

PAGES

452-459

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncb1708

DOI

http://dx.doi.org/10.1038/ncb1708

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18311132


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