This disease affects more than five million people worldwide, killing forty thousand of these every year. In a paper in the forthcoming issue of the open-access journal PLoS Medicine, researchers identified a protein called osteopontin that may play a key role in the lethal disease. Identification of this protein could lead to the development of new treatments for IPF.

Annie Pardo and colleagues, based in University Medical Centres in Pittsburgh and Mexico City, took samples from a number of people with IPF in order to analyse the pattern of gene expression in the lungs. They discovered that osteopontin was more prevalent in the lungs of people with the disease than those without it. Examining the role of this protein further, the researchers found that it increased the proliferation and movement of cells involved in lung fibrosis. These findings reinforce previous research that suggested mice are protected from a similar lung disease if they do not have the gene for osteopontin.

The results of the study are important because there is currently no effective medical treatment for this disease. The results suggest that treatment may be possible through drugs specifically directed against osteopontin. By highlighting the role of this protein, the study could also aid the early detection of a disease that is frequently misdiagnosed and little understood.

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The analyses of the embryonic stem cell lines and the computer comparisons of the mounds of resulting data required the efforts of scientists at four academic centers, two federal laboratories and three companies. Critical to the team's success was prescient support of cutting-edge technology development by the National Institutes of Health, support that enabled development of the technological infrastructure necessary for large-scale comparative research, particularly the Human Genome Project, says study co-author Mahendra Rao, M.B.B.S., Ph.D., of the Laboratory of Neurosciences at the National Institute on Aging.

The scientists used so-called GeneChip microarrays, or oligonucleotide arrays, to determine whether there were genetic differences between the early and the late batch of each of the stem cell lines, including whether any genes were present in extra copies. Depending on the gene affected, extra copies could lead to accelerated cell growth, increased cell death, or no measurable effect at all.

In addition to probing changes in the nuclear and mitochondrial DNA sequences and copy numbers, the researchers examined whether the cells' genetic material had shifts in marks that sit on genes and are passed from cell to cell during cell division. These so-called epigenetic marks -- in this case methyl groups on a gene region known as the promoter -- help control whether a gene is used by a cell to make proteins. The researchers determined the methylation status of 14 genes in each of the batches of stem cells; three of the genes did show different methylation patterns in late batches compared to early batches.

The scientists' analysis revealed that five of the nine cell lines had extra or fewer copies of at least one section of their genetic material in the late batch compared to the same cell line's early batch. Two of the nine lines had changes in their mitochondrial DNA over time, and all nine stem cell lines exhibited some shift in methylation of at least one of three genes. One of these genes, called RASSF1A, is also methylated in many cancers, but what effect the methylation has on the stem cells is unknown.

The team is already planning to conduct similar analyses of the remaining NIH-approved cell lines, but analysis of stem cell lines not available for use with federal funds will also be needed, the team members say.

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