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

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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300864/
https://www.ncbi.nlm.nih.gov/pubmed/35872784
http://dx.doi.org/10.3389/fmed.2022.873923
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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.
author_facet 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.
author_sort Raghubar, Arti M.
collection PubMed
description 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.
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spelling pubmed-93008642022-07-22 Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments 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. Front Med (Lausanne) Medicine 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. Frontiers Media S.A. 2022-07-07 /pmc/articles/PMC9300864/ /pubmed/35872784 http://dx.doi.org/10.3389/fmed.2022.873923 Text en Copyright © 2022 Raghubar, Pham, Tan, Grice, Crawford, Lam, Andersen, Yoon, Teoh, Matigian, Stewart, Francis, Ng, Healy, Combes, Kassianos, Nguyen and Mallett. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
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.
Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments
title Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments
title_full Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments
title_fullStr Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments
title_full_unstemmed Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments
title_short Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments
title_sort spatially resolved transcriptomes of mammalian kidneys illustrate the molecular complexity and interactions of functional nephron segments
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300864/
https://www.ncbi.nlm.nih.gov/pubmed/35872784
http://dx.doi.org/10.3389/fmed.2022.873923
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