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

Frontiers in Medicine

article

Arti M. Raghubar¹  Duy T. Pham⁵  Xiao Tan⁵  Laura F. Grice⁵  Joanna Crawford⁵  Pui Yeng Lam⁵  Stacey B. Andersen⁷  Sohye Yoon⁷  Siok Min Teoh⁹  Nicholas A. Matigian^1,10  Anne Stewart⁴  Leo Francis⁴  Monica S. Y. Ng¹  Helen G. Healy¹  Alexander N. Combes^1,12  Andrew J. Kassianos¹  Quan Nguyen⁵  Andrew J. Mallett³ 

[1] Kidney Health Service, Royal Brisbane and Women's Hospital;Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Health Support Queensland;Faculty of Medicine, University of Queensland;Anatomical Pathology, Pathology Queensland, Health Support Queensland;Institute for Molecular Bioscience, University of Queensland;School of Biomedical Sciences, The University of Queensland;Genome Innovation Hub, University of Queensland;UQ Sequencing Facility, Institute for Molecular Bioscience, University of Queensland;UQ Diamantina Institute, Faculty of Medicine, The University of Queensland;QCIF Facility for Advanced Bioinformatics, Institute for Molecular Bioscience, The University of Queensland;Nephrology Department, Princess Alexandra Hospital;Department of Anatomy and Developmental Biology, Stem Cells and Development Program, Monash Biomedicine Discovery Institute, Monash University;College of Medicine & Dentistry, James Cook University;Department of Renal Medicine, Townsville University Hospital

关键词: spatial transcriptomics;    kidney;    human;    mouse;    cell-cell interactions;   

DOI  :  10.3389/fmed.2022.873923

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Available transcriptomes of the mammalian kidney provide limited information on the spatial interplay between different functional nephron structures due to the required dissociation of tissue with traditional transcriptome-based methodologies. A deeper understanding of the complexity of functional nephron structures requires a non-dissociative transcriptomics approach, such as spatial transcriptomics sequencing (ST-seq). We hypothesize 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 the cell level. Here, we applied ST-seq in six mice 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 ( p adj < 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 provide a valuable resource for the kidney community that can be used to inform future research into this complex organ.

【 授权许可】

CC BY