In the early, online version of the Proceedings of the National Academy of Sciences, an international team led by investigators in Denmark describes optical mapping and whole-genome sequencing experiments on individual cells using a single-cell DNA extraction strategy based on microfluidic or nanofluidic chips. The researchers demonstrate that that on-chip optical mapping with denaturation-renaturation could provide a look at structural variants in individual cells from a colorectal cancer cell line, for example, revealed some features missed by single-cell genome sequencing. "[O]ptical mapping of the long-range features of single-cell genomes and sequencing of the short-range features may become complementary tools for the analysis of tumors," they write.
National Institutes of Health researchers explore potential human herpesvirus (HHV) contributions to neuroinflammatory conditions that fuel autoimmune conditions such as multiple sclerosis (MS). When the team inoculated marmosets with HHV-6A and HHV-6B intranasally, it found that the viruses hastened the course of experimental autoimmune encephalomyelitis — an MS-like condition — and was linked more robust immune responses, including proinflammatory CD8 cell expansions. "Our data support the hypothesis that viruses may act as triggers to lower the threshold for autoimmunity," the investigators note, "and warrant trials of antiviral interventions in early disease stages."
A University of Wisconsin team takes a look at mutations affecting the hematopoiesis regulator gene GATA2, which have been implicated in immunodeficiency, myelodysplastic syndrome, or acute myeloid leukemia. Using a quantitative chromatin immunoprecipitation assay to track chromatin occupancy and a genetic complementation assay aimed at assessing GATA-2 protein function in myeloid progenitor cells from mice carrying a mutation that dialed down GATA2 expression, the researchers found that GATA2 mutations implicated in conditions such as AML could bolster GATA-2 activity in the mutant mouse cells. The findings "transform the current paradigm that disease mutations are solely inhibitory, and ectopically low GATA-2 levels/activity constitute the disease mechanism," the authors say.