Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment

Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors associated with autonomic nerves. Here we use single-nuclei RNA-seq and bulk-tissue gene-expression data to characterize the cellular composition of PCPG and normal adrenal tissues, refine tumor gene-expression subtypes and make clinical and genotypic associations. We confirm seven PCPG gene-expression subtypes with significant genotype and clinical associations. Tumors with mutations in VHL, SDH-encoding genes (SDHx) or MAML3-fusions are characterized by hypoxia-inducible factor signaling and neoangiogenesis. PCPG have few infiltrating lymphocytes but abundant macrophages. While neoplastic cells transcriptionally resemble mature chromaffin cells, early chromaffin and neuroblast markers are also features of some PCPG subtypes. The gene-expression profile of metastatic SDHx-related PCPG indicates these tumors have elevated cellular proliferation and a lower number of non-neoplastic Schwann-cell-like cells, while GPR139 is a potential theranostic target. Our findings therefore clarify the diverse transcriptional programs and cellular composition of PCPG and identify biomarkers of potential clinical significance.Magnus Zethoven, Luciano Martelotto, Andrew Pattison, Blake Bowen, Shiva Balachander, Aidan Flynn, Fernando J. Rossello, Annette Hogg, Julie A.Miller, Zdenek Frysak, Sean Grimmond, Lauren Fishbein, Arthur S. Tischler, Anthony J. Gill, Rodney J. Hicks, Patricia L. M. Dahia, Roderick Clifton-Bligh, Karel Pacak, Richard W. Tothil

Natural and synthetic oligosaccharides in broiler chicken diets

This review presents findings on the influence of natural raffinose series oligosaccharides and synthetic (industrial) products on the productivity of broiler chicken. There is evidence of negative effects on animal health and productivity from the use of raffinose series oligosaccharides, but beneficial effects from synthetic oligosaccharides. Part of this contradiction may be due to differences in the chemical nature of the supplements, the level of supple-mentation or the duration of feeding. The future for synthetic oligosaccharides is bright, but further adoption of natural sources requires a greater understanding of their chemistry to facilitate the production of beneficial compounds and the elimination of detrimental fractions. Most current literature favours the inclusion of various oligosaccharides in the diet. The cost of production could be minimised by the use of natural ingredients which contain oligosaccharides, or by cheap synthetic products, sources of which are highlighted in this review. © World's Poultry Science Association 1998