March 3, 2011

Aliquots — research highlights from VUMC laboratories


A better picture of bone strength

There’s more to bone than just hard minerals like calcium. “Soft” components like collagen and collagen-bound water comprise more than half of bone’s content and are important for bone strength. X-ray based diagnostic tests (like CT and DXA – or “DEXA” – scans), which are used to assess bone strength and density, are sensitive only to the mineral portion of bone; the soft components are essentially invisible.

Mark Does, Ph.D., Jeffry Nyman, Ph.D., and colleagues investigated the utility of nuclear magnetic resonance (NMR) signals – the basis for MRI scans – for assessing the mechanical properties of bone samples from cadavers. They found that NMR signals were better predictors of several measures of bone strength than X-ray derived signals like DXA.

Although standard clinical MRI scanners do not detect the exact NMR signals used in this study, the results, reported Jan. 21 in PLoS ONE, suggest that if these measures are implemented on clinical scanners, MRI scans could provide a more complete assessment of fracture risk than X-ray based tests.

— Melissa Marino


Worm gene function? Check the map.

The roundworm C. elegans provides a simple yet representative model of development that depends on differential expression of a compact, well-described genome. Although the developmental origin of each C. elegans cell is fully described, a comparable gene expression map is not currently available.

David Miller, Ph.D., and colleagues have now produced a gene expression atlas for more than 30 different cell types and developmental stages. These results revealed that most worm genes are highly regulated across developmental stages and cell types. The researchers also detected a large number of novel genes of unknown function that comprise about 10 percent of the C. elegans genome.

The resulting spatial and temporal gene expression maps, reported in the February issue of Genome Research, provide a basis for establishing roles for individual genes in the development of specific cell types. The researchers also established online resources to facilitate the use of these data for future studies (

— Leigh MacMillan


Chasing Foxd3’s role in stem cells

Developing stem cell-based therapies to repair damaged tissues requires a clear understanding of the factors that maintain stem cell populations. Graduate student Nathan Mundell and Patricia Labosky, Ph.D., explored the role of the factor Foxd3 in neural crest cells, a population of cells that gives rise to a wide range of tissues including neurons, smooth muscle cells, and bone.

In the Feb. 15 issue of Development, they report that Foxd3 maintains neural crest cell multipotency (ability to become multiple adult tissues) and self-renewal. Mouse neural crest cells missing the Foxd3 gene did not develop into neural cell types and instead, formed smooth muscle cells in abnormal locations. Using single-cell analyses, the researchers found that Foxd3 suppressed neural crest cell differentiation into muscle-type cells and maintained neural crest in an uncommitted state.

The results add to previous studies from this team, which showed that Foxd3 maintains embryonic and trophoblast stem cell populations as well. Together, the findings suggest that Foxd3 may be a fundamental regulator of “stemness.”

— Leigh MacMillan


Enzyme protects against inflamed colon

Inflammation is beneficial when the body is fighting off an acute infection – but not so helpful when it becomes chronic. For patients with inflammatory bowel disease, persistent inflammation in the gastrointestinal tract increases the risk of colon cancer.

Jeremy Goettel, Ph.D., and colleagues examined the role of KSR1, an enzyme required for colon epithelial cell survival, during chronic inflammation of the colon. They crossed mice deficient in the anti-inflammatory molecule IL-10 (a model of spontaneous colitis) with mice deficient in KSR1.

The resulting double knockout mice developed accelerated severe colitis by 4 weeks of age, primarily due to loss of KSR1 in immune cell lineages. T helper cells missing KSR1 had increased interferon-gamma production, and administration of an interferon-gamma neutralizing antibody attenuated the severity of colitis in the double knockout mice.

The findings, reported in the January issue of Gastroenterology, suggest that strategies to increase KSR1 expression may be beneficial in dampening inflammatory responses.

— Melissa Marino


We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012