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: aliquots@vanderbilt.edu.
Keys to building new blood vessels
Angiogenesis – the formation of new blood vessels – occurs in both physiologic (wound healing) and pathologic (tumor growth) events. The interactions of blood vessel endothelial cells with the surrounding matrix, through cell receptors called integrins, regulate many steps of angiogenesis.
Ambra Pozzi, Ph.D., and colleagues previously showed that integrin a1b1, a major collagen receptor, plays a role in pathologic angiogenesis. To investigate how this integrin controls endothelial cell functions, the investigators made a variety of mutations in the intracellular “tail” of the a1 subunit and studied these mutants in cultured cells. They report in the Oct. 15 issue of Blood that specific amino acids in the a1 tail are critical for the activation of distinct signaling pathways and for integrin a1b1-dependent functions, including endothelial cell proliferation, migration, adhesion and tube formation. The studies could help determine whether preventing integrin a1b1-mediated signaling represents a valid therapeutic strategy for diseases characterized by uncontrolled angiogenesis.
To see the study, go <a href="http://bloodjournal.hematologylibrary.org/cgi/content/abstract/112/8/3242">here</a>.
— Leigh MacMillan
Foxd3 keeps stem cells young
Embryonic stem cells (ESCs) can develop into all the various types of adult cells, making them promising tools for regenerative therapies. But developing stem cell-based therapies requires a deeper understanding of the many factors that maintain the cells’ pluripotent, self-renewing state.
Patricia Labosky, Ph.D., and colleagues are investigating the role of one such factor, Foxd3, which they previously showed is required early in mouse development for establishing embryonic stem cells. To examine the protein’s role in maintaining these cells, the investigators generated mouse ESCs in which Foxd3 could be turned “off” by treating the cells with the drug tamoxifen. In the October issue of Stem Cells, they report that while Foxd3-deficient cells divide at the same rate as normal cells, they undergo increased levels of cell death. The mutant cells also show a decreased capacity to self-renew and a propensity to prematurely differentiate into more mature cell types. The results demonstrate that Foxd3 promotes stem cell self-renewal by repressing differentiation and keeping them in their pluripotent state.
To see the study, go <a href="http://stemcells.alphamedpress.org/cgi/content/abstract/26/10/2475">here</a>.
— Melissa Marino
A potential ‘achoo’ culprit
Allergies are on the rise in the United States, but the environmental factors that contribute to their development are not well understood. Recent evidence from animal models and epidemiological studies suggests that inhibition of the enzyme cyclooxygenase (COX) – with drugs such as indomethacin and acetaminophen, respectively – may boost allergic responses.
Weisong Zhou, Ph.D., and colleagues studied how COX inhibition affects allergy development in a mouse model. They found that COX inhibition during sensitization to the allergen – but not during the later challenge period – increased the allergic response (greater numbers of Th2 type immune cells in the spleen and higher levels of Th2 type cytokines). COX inhibition during sensitization also enhanced immune memory generation, another component of allergy development. The findings, reported in the Oct. 15 Journal of Immunology, suggest that COX inhibition during the initial exposure to allergens may increase the risk of development of allergic disorders.
To see the study, go <a href="http://www.jimmunol.org/cgi/content/abstract/181/8/5360">here</a>.
— Leigh MacMillan
Blood cells turn down wrong path
Chromosomal translocations – the rearrangement of pieces of different chromosomes – are seen in several types of leukemia. A translocation between chromosomes 16 and 21 is a rare cause of acute myeloid leukemia (AML), a blood cancer characterized by the overproduction of white blood cells of the myeloid lineage.
Scott Hiebert, Ph.D., and colleagues created mice lacking Mtg16 – the gene affected by this translocation – to investigate its role in the maturation of blood-forming stem cells. In the October issue of Molecular and Cellular Biology, they report that inactivation of Mtg16 skews the developmental path of these cells, increasing numbers of myeloid white blood cell progenitors and reducing numbers of progenitor cells that develop into platelets and red blood cells. Mtg16 inactivation also impaired the rapid expansion of the various types of stem and progenitor cells needed to replenish the blood during an emergency (e.g., blood loss). A better grasp of the normal functions of Mtg16 and related genes could improve our understanding of how acute leukemias develop, the researchers suggest.
To see the study, go <a href="http://mcb.asm.org/cgi/content/abstract/28/20/6234">here</a>.
— Melissa Marino
Past Aliquots
June 22, 2012
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