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Keeping stem cells strong
Date:5/21/2013

When infections occur in the body, stem cells in the blood often jump into action by multiplying and differentiating into mature immune cells that can fight off illness. But repeated infections and inflammation can deplete these cell populations, potentially leading to the development of serious blood conditions such as cancer. Now, a team of researchers led by biologists at the California Institute of Technology (Caltech) has found that, in mouse models, the molecule microRNA-146a (miR-146a) acts as a critical regulator and protector of blood-forming stem cells (called hematopoietic stem cells, or HSCs) during chronic inflammation, suggesting that a deficiency of miR-146a may be one important cause of blood cancers and bone marrow failure.

The team came to this conclusion by developing a mouse model that lacks miR-146a. RNA is a polymer structured like DNA, the chemical that makes up our genes. MicroRNAs, as the name implies, are a class of very short RNAs that can interfere with or regulate the activities of particular genes. When subjected to a state of chronic inflammation, mice lacking miR-146a showed a decline in the overall number and quality of their HSCs; normal mice producing the molecule, in contrast, were better able to maintain their levels of HSCs despite long-term inflammation. The researchers' findings are outlined in the May 21 issue of the new journal eLIFE.

"This mouse with genetic deletion of miR-146a is a wonderful model with which to understand chronic-inflammation-driven tumor formation and hematopoietic stem cell biology during chronic inflammation," says Jimmy Zhao, the lead author of the study and a MD/PhD student in the Caltech laboratory of David Baltimore, the Robert Andrews Millikan Professor of Biology. "It was surprising that a single microRNA plays such a crucial role. Deleting it produced a profound and dramatic pathology, which clearly highlights the critical and indispensable function of miR-146a in
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Contact: Deborah Williams-Hedges
debwms@caltech.edu
626-395-3227
California Institute of Technology
Source:Eurekalert

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