Single-cell mRNA profiling reveals changes in solute carrier expression and suggests a metabolic switch during zebrafish pronephros development

Abstract

Developing organisms need to adapt to environmental variations as well as to rapid changes in substrate availability and energy demands imposed by fast-growing tissues and organs. Little is known about the adjustments that kidneys undergo in response to these challenges. We performed single-cell RNA sequencing of zebrafish pronephric duct cells to understand how the developing kidney responds to changes in filtered substrates and intrinsic energy requirements. We found high levels of glucose transporters early in development and increased expression of monocarboxylate transporters at later times. This indicates that the zebrafish embryonal kidney displays a high glucose transporting capacity during early development, which is replaced by the ability to absorb monocarboxylates and amino acids at later stages. This change in transport capacity was accompanied by upregulation of mitochondrial carriers, indicating a switch to increased oxidative phosphorylation to meet the increasing energy demand of a developing kidney.

Control of Directed Cell Migration after Tubular Cell Injury by Nucleotide Signaling

“…Single-cell RNA sequencing revealed expression of zebrafish p2ry2 along the entire pronephros [ 21 ], while members of the p2x and other members of the p2y gene family were expressed at lower levels ( Figure 4 A). Three different genes encode for zebrafish p2ry2 ( p2ry2 .1, p2ry2.2 , and p2ry2.3 ).…”

“…However, it is currently unknown how tubular epithelial cells sense damage and how the migratory response is coordinated. Single-cell RNA sequencing and microarray analysis revealed upregulation of P1 and P2 purinergic family members in the pronephros of two-day-old zebrafish embryos [ 7 , 21 ], suggesting that ATP and ATP metabolites are involved in the signaling events in response to injury.…”

“…The RNAseq data are publicly available and the analysis has been previously described [ 21 ]. The heat map was generated in Excel.…”

“…Whole-mount in situ hybridization (WISH) was performed as previously described [ 21 ]. RNA probes against p2ry2.1 , p2ry2.2 , p2ry2.3 , ada , ada2a , ada2b , adal , adora1a , adora1b , adora2b , adora2aa and adora2ab were generated from a cDNA library from 1–2-day-old embryos.…”

Interactions of Environmental Chemicals and Natural Products With ABC and SLC Transporters in the Digestive System of Aquatic Organisms

“…In fish, SLCs play an important role in organismal development and transport of endogenous compounds to allow for proper development of swim bladders ( Kim et al, 2020 ), inner ears ( Liu et al, 2015 ), kidneys ( Schoels et al, 2021 ), and normal development of embryos ( Takesono et al, 2012 ). In addition, SLCs play a crucial role in intestinal absorption and transport of amino acids and other physiological compounds, including thyroid hormones ( Arjona et al, 2011 ; Muzzio et al, 2014 ), iron ( Cooper et al, 2007 ), zinc ( Yan et al, 2012 ; Jiang et al, 2014 ), coenzyme-A ( Kim et al, 2020 ), and amino acids and peptides ( Romano et al, 2006 , 2014 ; Verri et al, 2010 , 2017 ; Margheritis et al, 2013 ; Rimoldi et al, 2015 ; Song et al, 2017 ; To et al, 2019 ; Vacca et al, 2019 ).…”