Mapping the cellular landscape of Atlantic salmon head kidney by single cell and single nucleus transcriptomics

• Published in: Fish & Shellfish Immunology
• Main Authors: Andresen, Adriana M.S., Taylor, Richard S., Grimholt, Unni, Daniels, Rose Ruiz, Sun, Jianxuan, Dobie, Ross, Henderson, Neil C., Martin, Samuel A.M., Macqueen, Daniel J., Fosse, Johanna H.
• Other Authors: Biotechnology and Biological Sciences Research Council, Norwegian Veterinary Institute, University of Edinburgh, Institute of Aquaculture, University of Aberdeen, orcid:0009-0006-1478-7221, orcid:0000-0002-2273-4094, orcid:0000-0003-0289-6317, orcid:0000-0001-5837-5006
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier BV 2024
• Subjects: Atlantic Salmon; Single cell RNA sequencing; Single nucleus RNA sequencing; Cellular heterogeneity; Head kidney; Marker genes; Atlantic salmon; Salmo salar
• Online Access: http://hdl.handle.net/1893/35862; https://doi.org/10.1016/j.fsi.2024.109357; http://dspace.stir.ac.uk/retrieve/3c9ce768-c0e9-4b94-b517-d88dfb91562a/Mapping%20the%20cellular%20landscape%20of%20Atlantic%20salmon%20head%20kidney%20by%20single%20cell%20and%20single%20nucleus%20transcriptomics.pdf

Single-cell transcriptomics is the current gold standard for global gene expression profiling, not only in mammals and model species, but also in non-model fish species. This is a rapidly expanding field, creating a deeper understanding of tissue heterogeneity and the distinct functions of individual cells, making it possible to explore the complexities of immunology and gene expression on a highly resolved level. In this study, we compared two single cell transcriptomic approaches to investigate cellular heterogeneity within the head kidney of healthy farmed Atlantic salmon (Salmo salar). We compared 14,149 cell transcriptomes assayed by single cell RNA-seq (scRNA-seq) with 18,067 nuclei transcriptomes captured by single nucleus RNA-Seq (snRNA-seq). Both approaches detected eight major cell populations in common: granulocytes, heamatopoietic stem cells, erythrocytes, mononuclear phagocytes, thrombocytes, B cells, NK-like cells, and T cells. Four additional cell types, endothelial, epithelial, interrenal, and mesenchymal cells, were detected in the snRNA-seq dataset, but appeared to be lost during preparation of the single cell suspension submitted for scRNA-seq library generation. We identified additional heterogeneity and subpopulations within the B cells, T cells, and endothelial cells, and revealed developmental trajectories of heamatopoietic stem cells into differentiated granulocyte and mononuclear phagocyte populations. Gene expression profiles of B cell subtypes revealed distinct IgM and IgT-skewed resting B cell lineages and provided insights into the regulation of B cell lymphopoiesis. The analysis revealed eleven T cell sub-populations, displaying a level of T cell heterogeneity in salmon head kidney comparable to that observed in mammals, including distinct subsets of cd4/cd8-negative T cells, such as tcrγ positive, progenitor-like, and cytotoxic cells. Although snRNA-seq and scRNA-seq were both useful to resolve cell type-specific expression in the Atlantic salmon head kidney, the snRNA-seq pipeline ...