Three dimensional multiscalar neurovascular nephron connectivity map of the human kidney across the lifespan

Abstract The human kidney maintains homeostasis through a complex network of up to a million nephrons, its fundamental tissue units. Using innovative tissue processing and light sheet fluorescence microscopy, we mapped the 3D neurovascular connectivity of nephrons to understand how their structural...

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Main Authors: Liam McLaughlin, Bo Zhang, Siddharth Sharma, Amanda L. Knoten, Madhurima Kaushal, Jeffrey M. Purkerson, Heidie L. Huyck, Gloria S. Pryhuber, Joseph P. Gaut, Sanjay Jain
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60435-8
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author Liam McLaughlin
Bo Zhang
Siddharth Sharma
Amanda L. Knoten
Madhurima Kaushal
Jeffrey M. Purkerson
Heidie L. Huyck
Gloria S. Pryhuber
Joseph P. Gaut
Sanjay Jain
author_facet Liam McLaughlin
Bo Zhang
Siddharth Sharma
Amanda L. Knoten
Madhurima Kaushal
Jeffrey M. Purkerson
Heidie L. Huyck
Gloria S. Pryhuber
Joseph P. Gaut
Sanjay Jain
author_sort Liam McLaughlin
collection DOAJ
description Abstract The human kidney maintains homeostasis through a complex network of up to a million nephrons, its fundamental tissue units. Using innovative tissue processing and light sheet fluorescence microscopy, we mapped the 3D neurovascular connectivity of nephrons to understand how their structural organization enables coordinated functions like filtration, absorption, and blood pressure regulation. Our analysis revealed developmental changes in glomerular orientation, density, volume, and innervation from birth through aging. We discovered an extensive nerve network connecting different nephron segments and organizing glomeruli into distinct communities. These communities are linked through “mother glomeruli” that serve as control centers, creating a repeating pattern throughout the cortex. This sophisticated neural organization, which is underdeveloped in newborn kidneys and disrupted in conditions like diabetes and hydronephrosis, appears to facilitate synchronized responses to maintain fluid balance. The findings provide insights into how the kidney’s structural architecture enables coordinated function across its numerous nephrons.
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issn 2041-1723
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spelling doaj-art-285db5ec60ad4e36aa8c88fc20dcf6492025-08-20T03:10:34ZengNature PortfolioNature Communications2041-17232025-06-0116112210.1038/s41467-025-60435-8Three dimensional multiscalar neurovascular nephron connectivity map of the human kidney across the lifespanLiam McLaughlin0Bo Zhang1Siddharth Sharma2Amanda L. Knoten3Madhurima Kaushal4Jeffrey M. Purkerson5Heidie L. Huyck6Gloria S. Pryhuber7Joseph P. Gaut8Sanjay Jain9Department of Medicine, Washington University School of MedicineDepartment of Medicine, Washington University School of MedicineDepartment of Medicine, Washington University School of MedicineDepartment of Medicine, Washington University School of MedicineDepartment of Medicine, Washington University School of MedicineDepartment of Pediatrics, University of Rochester Medical CenterDepartment of Pediatrics, University of Rochester Medical CenterDepartment of Pediatrics, University of Rochester Medical CenterDepartment of Pathology & Immunology, Washington University School of MedicineDepartment of Medicine, Washington University School of MedicineAbstract The human kidney maintains homeostasis through a complex network of up to a million nephrons, its fundamental tissue units. Using innovative tissue processing and light sheet fluorescence microscopy, we mapped the 3D neurovascular connectivity of nephrons to understand how their structural organization enables coordinated functions like filtration, absorption, and blood pressure regulation. Our analysis revealed developmental changes in glomerular orientation, density, volume, and innervation from birth through aging. We discovered an extensive nerve network connecting different nephron segments and organizing glomeruli into distinct communities. These communities are linked through “mother glomeruli” that serve as control centers, creating a repeating pattern throughout the cortex. This sophisticated neural organization, which is underdeveloped in newborn kidneys and disrupted in conditions like diabetes and hydronephrosis, appears to facilitate synchronized responses to maintain fluid balance. The findings provide insights into how the kidney’s structural architecture enables coordinated function across its numerous nephrons.https://doi.org/10.1038/s41467-025-60435-8
spellingShingle Liam McLaughlin
Bo Zhang
Siddharth Sharma
Amanda L. Knoten
Madhurima Kaushal
Jeffrey M. Purkerson
Heidie L. Huyck
Gloria S. Pryhuber
Joseph P. Gaut
Sanjay Jain
Three dimensional multiscalar neurovascular nephron connectivity map of the human kidney across the lifespan
Nature Communications
title Three dimensional multiscalar neurovascular nephron connectivity map of the human kidney across the lifespan
title_full Three dimensional multiscalar neurovascular nephron connectivity map of the human kidney across the lifespan
title_fullStr Three dimensional multiscalar neurovascular nephron connectivity map of the human kidney across the lifespan
title_full_unstemmed Three dimensional multiscalar neurovascular nephron connectivity map of the human kidney across the lifespan
title_short Three dimensional multiscalar neurovascular nephron connectivity map of the human kidney across the lifespan
title_sort three dimensional multiscalar neurovascular nephron connectivity map of the human kidney across the lifespan
url https://doi.org/10.1038/s41467-025-60435-8
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