AUTHOR=Raghubar Arti M. , Pham Duy T. , Tan Xiao , Grice Laura F. , Crawford Joanna , Lam Pui Yeng , Andersen Stacey B. , Yoon Sohye , Teoh Siok Min , Matigian Nicholas A. , Stewart Anne , Francis Leo , Ng Monica S. Y. , Healy Helen G. , Combes Alexander N. , Kassianos Andrew J. , Nguyen Quan , Mallett Andrew J. 

TITLE=Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments

JOURNAL=Frontiers in Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.873923

DOI=10.3389/fmed.2022.873923

ISSN=2296-858X

ABSTRACT=Available transcriptomes of the mammalian kidney provide limited information on the spatial interplay between different functional nephron structures due to required dissociation of tissue with traditional transcriptomic based methodologies. A deeper understanding of the complexity of functional nephron structures requires a non-dissociative transcriptomics approach like spatial transcriptomics sequencing (ST-seq). We hypothesis that the application of ST-seq in normal mammalian kidneys will give transcriptomic insights within and across species of physiology at the functional structure level and cellular communication at cell level.
Here, we applied ST-seq in six mouse and four human kidneys that were histologically absent of any overt pathology. We defined the location of specific nephron structures in the captured ST-seq datasets using three lines of evidence: pathologist’s annotation, marker gene expression and integration with public single-cell and/or single-nucleus RNA-sequencing datasets. We compared the mouse and human cortical kidney regions. In the human ST-seq datasets, we further investigated the cellular communication within glomeruli and regions of proximal tubules-peritubular capillaries by screening for co-expression of ligand-receptor gene pairs. 
Gene expression signatures of distinct nephron structures and microvascular regions were spatially resolved within the mouse and human ST-seq datasets. We identified 7,370 differentially expressed genes (padj <0.05) distinguishing species, suggesting changes in energy production and metabolism in mouse cortical regions relative to human kidneys. Hundreds of potential ligand-receptor interactions were identified within glomeruli and regions of proximal tubules-peritubular capillaries, including known and novel interactions relevant to kidney physiology. Our application of ST-seq to normal human and murine kidneys confirms current knowledge and localization of transcripts within the kidney. Furthermore, the generated ST-seq datasets provides a valuable resource for the kidney community that can be used to inform future research into this complex organ.