Adult stem cell changes underlie rare genetic disease associated with acceler...(xamined the effects of progerin on gene ...),Health

Date:3/2/2008

xamined the effects of progerin on gene expression in a laboratory model of HGPS. They found that progerin activates genes involved in the Notch signaling pathway, a major regulator of stem cell differentiation -- the process by which stem cells give rise to the mature cells that make up different tissues.

Because most of the tissues affected by HGPS (e.g., skin, fat, muscles, bone, and blood vessels) arise from a common developmental pathway, Misteli and Scaffidi looked at the effects of progerin on adult mesenchymal stem cells, the common cellular ancestor of these tissue types. An adult stem can renew itself, and can differentiate to yield the major specialized cell types of the tissue or organ. Their experiments revealed that progerin profoundly affects the fate of these stem cells, greatly skewing the rate at which they mature into different tissues. For instance, progerin-producing stem cells showed accelerated maturation into bone but failed to develop into fat. This could explain two of the distinguishing clinical features of HGPS: abnormal bone growth and an almost complete loss of the fatty tissues normally found just beneath the skin. The researchers were able to mimic the progerins effects in these stem cells by experimentally activating the same components of the Notch pathway targeted by progerin.

Taken together, the results of these experiments provide a new window into the biology behind the clinical features of HGPS. They may also hold relevance for understanding the biology of normal aging. Progerin is present at low levels in the cells of healthy people, said Misteli. One could envision a scenario in which progerins effects on the Notch pathway and, by extension, on adult stem cells could, over time, lead to many of the tissue changes we commonly associate with the aging process.

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Contact: NCI Press Officers ncipressofficers@mail.nih.gov 301-496-6641 NIH/National Cancer Institute Source:Eurekalert

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