A cell atlas of the fly kidney

Abstract

Like humans, insects rely on precise regulation of their internal environments to survive. The insect renal system consists of Malpighian tubules and nephrocytes that share similarities to the mammalian kidney. Studies of the Drosophila Malpighian tubules and nephrocytes have provided many insights into our understanding of the excretion of waste products, stem cell regeneration, protein reabsorption, and as human kidney disease models. Here, we analyzed single-nucleus RNA sequencing (snRNA-seq) data sets to characterize the cell types of the adult fly kidney. We identified 11 distinct clusters representing renal stem cells (RSCs), stellate cells (SCs), regionally specific principal cells (PCs), garland nephrocyte cells (GCs) and pericardial nephrocytes (PNs). Analyses of these clusters revealed many new interesting features. For example, we found a new, previously unrecognized cell cluster: lower segment PCs that express Esyt2. In addition, we find that the SC marker genes RhoGEF64c, Frq2, Prip and CG10939 regulate their unusual cell shape. Further, we identified transcription factors specific to each cluster and built a network of signaling pathways that are potentially involved in mediating cell-cell communication between Malpighian tubule cell types. Finally, cross-species analysis allowed us to match the fly kidney cell types to mouse kidney cell types and planarian protonephridia - knowledge that will help the generation of kidney disease models. To visualize this dataset, we provide a web-based resource for gene expression in single cells (https://www.flyrnai.org/scRNA/kidney/). Altogether, our study provides a comprehensive resource for addressing gene function in the fly kidney and future disease studies.

FlyAtlas 2 in 2022: enhancements to the Drosophila melanogaster expression atlas

“…With the advent of single-cell transcriptomics, providing data on both whole organisms ( 13 ) and individual tissues ( 7 , 19 , 20 ), it is worth emphasising some of the reasons why tissue transcriptomic atlases continue to be useful. For example, it has been demonstrated that whole-organism transcriptomics can severely under-represent tissue-specific expression ( 1 ).…”

A protective role forDrosophilaFilamin in nephrocytes via Yorkie mediated hypertrophy

“…However, in recent studies cubilin and amnionless have been identified to be expressed in mammalian podocytes and to be important for nephrocyte diaphragm remodelling in nephrocytes ( Prabakaran et al, 2012 ; Gianesello et al, 2017 ; Atienza-Manuel et al, 2021 ). Moreover, according to single nucleus RNA-seq in adult fly kidneys, nephrocytes do not show an overlap with murine proximal tubular cells, but with podocytes and parietal epithelium ( Xu et al, 2021 Preprint ). The recent data and several studies using nephrocytes support the concept of nephrocytes as podocyte equivalent, but similarities to proximal tubular cells cannot be excluded.…”

From whole bodies to single cells: A guide to transcriptomic approaches for ecology and evolutionary biology

“…The assessment of transcriptional profiles of distinct cell types has resulted in the development of single cell atlases across tissues, conditions, developmental stages (e.g. Allen et al, 2020;Brunet Avalos et al, 2019;Chen et al, 2021;Corrales et al, 2022;Hu, Tattikota, et al, 2021;Karaiskos et al, 2017;Li et al, 2022;Najle et al, 2023;Papatheodorou et al, 2020;Suo et al, 2022;Xu et al, 2021) and even for entire organisms (Li et al, 2022). Such single cell atlases can directly be used to ask whether genes identified in bulk RNAseq approaches may be expressed in specific cell types.…”