Combined transcriptome and proteome profiling reveal cell-type-specific functions of Drosophila garland and pericardial nephrocytes
Drosophila nephrocytes are specialised cells that share critical functional, morphological, and molecular features with podocytes of the mammalian kidney, including the slit diaphragm, which is a functional filtration barrier. Accordingly, nephrocytes are considered highly suitable invertebrate models for glomerular disease in humans. In this study, we established a method to individually isolate the garland and pericardial nephrocytes from Drosophila of different developmental stages. This allowed us to collect nephrocyte samples that were devoid of any contamination by other cell types. We used a combination of mass spectrometry-based proteomics and RNA-Seq-based transcriptomics to characterise the proteome and transcriptome of the respective cells in an integrated manner. In addition to identifying a set of factors that were expressed exclusively in nephrocytes, we observed characteristic changes in the cellular proteome and transcriptome as a consequence of ageing. Furthermore, functional enrichment analyses suggested that larval and adult nephrocytes fulfil distinct physiological functions, which was also indicated for garland and pericardial nephrocytes in adult animals. In addition, the latter cells were characterised by transcriptomic and proteomic profiles that were suggestive of a cell-type-specific energy metabolism. Finally, both types of nephrocytes displayed transcriptomic signatures that indicated elevated immune signalling, implying that nephrocytes are immune competent. The data generated in this study may represent a valuable basis for a more specific application of the Drosophila model system in the analysis of renal cell function in health and disease. Overall design: Dissected nephrocytes (pericardial and garland cells) were used for proteomic and transcriptomic analysis. This included nephrocytes from larvae and adults of different age.