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PNAS Papers on Pancreatic Cells, Honey Bee Bacteriophages, Drug-Resistant Prostate Cancer

Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.

For a paper scheduled to appear in PNAS this week, researchers from the University of Miami and other centers in the US, the Netherlands, and Spain present findings from a single-cell RNA sequencing study of cell-sorted progenitor-like cells found in human pancreatic ducts. Based on transcriptome data for almost 4,900 individual pancreatic ductal cells sorted from human non-endocrine pancreatic tissues donated by three individuals, the team found pancreatic cell sub-populations falling in broad tissue-related groups with a range of differentiation stages. "Our data confirm the paradigm-shifting notion that specific lineages, long thought to be case in stone, are in fact in a state of flux between differentiation stages," the authors report, arguing that their results "indicate that progenitors might be activated in situ for therapeutic purposes."

A team from Belgium and the US takes a look at the prokaryote-associated viruses, or bacteriophages, found in the honey bee Apis mellifera. Using deep sequencing, the researchers tallied DNA- and RNA-based "prokaryotic viruses" in samples from hundreds of healthy or weakened Flemish honey bee colonies that were collected in 2012 and 2013 for the EpiloBEE project, uncovering a diverse bacteriophage collection that contained viruses carrying secondary metabolic genes. "The vast majority of the prokaryotic viral populations are novel at the genus level, and most of the encoded proteins comprise unknown functions," they report. "Nevertheless, genomes of bacteriophages were predicted to infect nearly every major bee gut bacterium, and functional annotation and auxiliary metabolic gene discovery imply the potential to influence microbial metabolism."

An Oregon Health and Science University-led team outlines molecular features found in advanced castration-resistant prostate cancer (CRPC) cases resistant to the androgen receptor antagonist drug enzalutamide. As part of a Phase II trial of enzalutamide in metastatic CRPC, the team did targeted DNA sequencing and/or RNA sequencing on available samples from the three dozen trial participants. By analyzing the mutation and expression data in up to 26 biopsies from these cases, they saw an uptick in "stemness" genes in tumors from the metastatic CRPC cases with poor enzalutamide response, along with a rise in TP53 gene mutations and a decline in androgen receptor (AR) activity. "Transcriptional profiling identified specific gene sets — including those linked to reduced AR transcriptional activity and a stemness program — that were activated in non-responders," the authors write, adding that these and other findings "suggest that patients whose tumors harbor this program should be considered for clinical trials testing rational agents to overcome de novo enzalutamide resistance."