UCSF Journal Club: Recent Research from UCSF Scientists
Alexandra Greer
Science Editor
VIROLOGY: Strong human endogenous retrovirus (HERV)-specific T cell responses are associated with control of HIV-1 in chronic infection. Sengupta, D., et al. (Nixon) Journal of Virology. Apr 27. [Epub ahead of print]
A huge portion of our genome contains the remnants of retroviruses that became stuck in our DNA ages ago and have long since become inactive due to years of accrued mutations. These remnants are called human endogenous retroviruses (HERVs) and have not been found to replicate, but rather sit dormant in our cells. In the Nixon lab at UCSF, scientists have shown that HIV activates HERVs lying latent in the genome and initiates transcription of HERV proteins (but not replication). This results in the generation of CD8+ killer T-cells specific for HERV protein-expressing cells. Here, the researchers wanted to determine whether HERV-specific T-cells were maintained even in chronic infection, and whether this T-cell pool correlated with disease state (or the lack of a disease state). Indeed, HERV specific T-cells were found even in chronic infection and were associated with a stronger CD4+ T-cell response and a lower viral load. Given that HERVs are found in the cells of all humans and are activated upon HIV infection (and even in chronic infection), this may prove a worthwhile HIV vaccine target.
STEM CELL BIOLOGY: Differentiation of human embryonic stem cells into pancreatic endoderm in patterned size-controlled clusters. Van Hoof, D.; Mendelsohn, A.D.; Seerke, R.; Desai, T.A.; German, M.S. Stem Cell Research. 6(3):276-85.
In type I diabetes, the immune system mistakenly attacks β cells of the pancreatic islets, resulting in islet destruction and the loss of insulin production. One active area of diabetes research is therefore the development of β cells and islets from stem cells for transplantation into patients whose islets have been destroyed. One difficulty in developing these cells is that they require specific living arrangements: they grow best when clustered, but must remain in small clusters to promote the most efficient nutrient and gas exchange. Here, researchers controlled the size of cell clusters by promoting their adhesion to coverslips with dots of laminin 120 um in diameter. Stem cells seeded onto the coverslips formed 3-dimensional aggregates of uniform size that could then be differentiated into pancreatic endoderm. Not only does this provide a useful form of controlling pancreatic precursor aggregate size, but may prove useful in controlling aggregate size for other ex vivo tissue development.
STEM CELL RESEARCH: Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Ohi, Y., et al. (Ramalho-Santos) Nature Cell Biology. Apr 17. [Epub ahead of print]
Recently, controversy has developed surrounding the utility of induced pluripotent stem cells (iPS) – cells that begin as normal body cells (such as skin, liver or immune cells) but are reprogrammed to become a less differentiated, pluripotent state. Scientists have reported that despite reprogramming, iPS cells retain some of the gene expression of their original tissue. In this paper, researchers found that reprogrammed cells from multiple tissues exhibited incomplete silencing of tissue-specific genes, due to incomplete promoter DNA methylation. Furthermore, they found that the incompletely silenced genes were more isolated than the efficiently silenced tissue-specific genes, indicating that silencing machinery may have difficulty in methylating isolated active genes. The authors point out that tissue-specific gene expression may not be all bad, however – as the complete silencing of the somatically expressed C9orf64 during reprogramming actually resulted in less efficient stem cell generation.
For comments or paper suggestions, email Alex at Alexandra.Greer@ucsf.edu.
This article appeared in the May 5, 2011 issue of Synapse.
