Researchers from the University of California, San Francisco, and elsewhere describe a gene editing-based, loss-of-function strategy to screen for human immune system regulators. Using "single guide RNA lentiviral infection with Cas9 protein electroporation," or SLICE, in combination with single-cell RNA sequencing, the team searched for regulatory contributors that stimulate or stymie primary human T cell activity in a series of experiments that included a screen done in the presence of a metabolite known for its immunosuppressive effects. "Taken together, these studies provide a rich resource of gene pathways that can be targeted to tune human T cell responses as well as a broadly applicable platform to probe primary human T cell biology at genome-scale," the authors write.
A Scripps Research Institute-led team takes a closer look at a cardiovascular disease-related locus on chromosome 9 with the help of TALEN-based haplotype editing. After collecting samples from individuals with or without coronary artery disease-associated variants in the region, the researchers produced induced pluripotent stem cells, which were subsequently differentiated into vascular smooth muscle cells and characterized by haplotype editing or deletion, functional assays, RNA sequencing, and network analyses. Lopping out the risky haplotype seemed to restore vascular smooth muscle cell stability, for example, but they saw risky cell phenotypes after introducing a heart disease-related long non-coding RNA into otherwise healthy cells. GenomeWeb has more on this, here.
Finally, researchers from Denmark, France, Sweden, and elsewhere explore ancient plague patterns by sequencing Yersinia pestis isolates from a 4,900-year-old Swedish gravesite, as GenomeWeb previously reported. In addition to demonstrating that this ancient version of Y. pestis had pathogenic features, the team used phylogenetics, molecular clock analyses, and comparative genomics to put the Swedish plague isolate in historical context, fleshing out possible Y. pestis transmission routes in Neolithic Europe. "These analyses revealed that multiple and independent lineages of Y. pestis branched and expanded across Eurasia during the Neolithic decline," the study's authors explain, "spreading most likely through early trade networks rather than massive human migrations."