Approaching an Endgame? Telomerase Defects Shed Light on Pluripotency
The telomere is the region of DNA at the end of chromosomes that protects them and allows replication to proceed to the end of the chromosome. At each DNA replication cycle, the telomeres are shortened and an enzyme called telomerase elongates the shortened telomere. Defects in telomere maintenance are associated with cancer, aging, and diseases such as Dyskeratosis congenital (DC). In order to investigate DC, a telomere maintenance disease, and the impact of defects in telomerase function on iPS cell pluripotency, HSCI Executive Committee member George Daley and colleagues studied telomerase function in iPS cells from patients with DC. They found that iPS cells from DC patients were able to overcome their telomerase defect and that up-regulation of the defective telomerase component is a feature of pluripotency. These results have exciting implications for our understanding of factors involved in pluripotency as well as suggest that increasing expression of the defective telomerase component in DC patients may be a feasible therapeutic approach.
Agarwal, S., Loh, Y.H., McLoughlin, E.M., Huang, J., Park, I.H., Miller, J.D., Huo, H., Okuka, M., Dos Reis, R.M., Loewer, S., Ng, H.H., Keefe, D.L., Goldman, F.D., Klingelhutz, A.J., Liu, L., Daley, G.Q. (2010). Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 464, 292-6.
Good Cells, Bad Neighborhood
The stem cell niche, the microenvironment in which stem cells are found, interacts with stem cells to regulate their fate. In a study examining how mesenchymal stem cells in the stem cell niche modulate hematopoiesis, the creation of the components in blood, HSCI Co-director David Scadden and fellow researchers examined the effects that a mutation in the cells that made up the niche had on the hematopoietic function of the stem cells in the niche. The scientists found that even though the cells in the niche did not have the same mutation as the cells that made up the niche, they had acquired a number of other mutations, including one leading to a predisposition to bone marrow failure and leukemia. From these studies, the researchers learned that genetic abnormalities in certain niche cells can cause disease in the stem cells that occupy the niche. This evidence supports the idea of niche-induced oncogenesis, enhances our knowledgebase of cancer-initiating and cancer-promoting events, and expands our potential repertoire of therapeutic targets.
Raaijmakers, M.H., Mukherjee, S., Guo, S., Zhang, S., Kobayashi,T., Schoonmaker, J.A., Ebert, B.L., Al-Shahrour, F., Hasserjian, R.P., Scadden, E.O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J.M., Scadden, D.T.(2010) Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. Mar 21. [Epub ahead of print]