{
    "abstract": "Therapies targeting blood vessels hold promise for autosomal dominant polycystic kidney disease (ADPKD), the most common inherited disorder causing kidney failure. However, the onset and nature of kidney vascular abnormalities in ADPKD are poorly defined. Accordingly, we employed a combination of single-cell transcriptomics; three-dimensional imaging with geometric, topological and fractal analyses; and multimodal magnetic resonance imaging with arterial spin labelling to investigate aberrant microvasculature in ADPKD kidneys. Within human ADPKD kidneys with advanced cystic pathology and excretory failure, we identified a molecularly distinct blood microvascular subpopulation, characterised by impaired angiogenic signalling and metabolic dysfunction, differing from endothelial injury profiles observed in non-cystic human kidney diseases. Next, Pkd1 mutant mouse kidneys were examined postnatally, when cystic pathology is well established, but before excretory failure. An aberrant endothelial subpopulation was also detected, concurrent with reduced cortical blood perfusion. Disorganised kidney cortical microvasculature was also present in Pkd1 mutant mouse fetal kidneys when tubular dilation begins. Thus, aberrant features of cystic kidney vasculature are harmonised between human and mouse ADPKD, supporting early targeting of the vasculature as a strategy to ameliorate ADPKD progression.",
    "authors": [
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nUCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.\nSpecialised Foundation Programme in Research, NHS East of England, Cambridge CB21 5XB, UK.",
            "firstname": "Daniyal J",
            "initials": "DJ",
            "lastname": "Jafree"
        },
        {
            "affiliation": "UCL Centre for Advanced Biomedical Imaging, University College London, London WC1E 6DD, UK.",
            "firstname": "Charith",
            "initials": "C",
            "lastname": "Perera"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.",
            "firstname": "Mary",
            "initials": "M",
            "lastname": "Ball"
        },
        {
            "affiliation": "UCL Centre for Advanced Biomedical Imaging, University College London, London WC1E 6DD, UK.",
            "firstname": "Daniele",
            "initials": "D",
            "lastname": "Tolomeo"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nUCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.",
            "firstname": "Gideon",
            "initials": "G",
            "lastname": "Pomeranz"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nUCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.",
            "firstname": "Laura",
            "initials": "L",
            "lastname": "Wilson"
        },
        {
            "affiliation": "Central Laser Facility, Science and Technologies Facilities Council, UK Research and Innovation, Didcot OX11 0QX, UK.",
            "firstname": "Benjamin",
            "initials": "B",
            "lastname": "Davis"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nUCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.",
            "firstname": "William J",
            "initials": "WJ",
            "lastname": "Mason"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nLymphovascular Medicine and Translational 3D-Histopathology Research Group, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin 10117, Germany.\nBerlin Institute of Health at Charit\u00e9-Universit\u00e4tsmedizin Berlin, BIH Center for Regenerative Therapies, Berlin 10117, Germany.",
            "firstname": "Eva Maria",
            "initials": "EM",
            "lastname": "Funk"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nUCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.",
            "firstname": "Maria",
            "initials": "M",
            "lastname": "Kolatsi-Joannou"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.",
            "firstname": "Radu",
            "initials": "R",
            "lastname": "Polschi"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nUCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.",
            "firstname": "Saif",
            "initials": "S",
            "lastname": "Malik"
        },
        {
            "affiliation": "Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge CB2 1TN, UK.\nWellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK.",
            "firstname": "Benjamin J",
            "initials": "BJ",
            "lastname": "Stewart"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nUCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.",
            "firstname": "Karen L",
            "initials": "KL",
            "lastname": "Price"
        },
        {
            "affiliation": "Mathematical Sciences Research Centre, Queen's University Belfast, Belfast BT7 1NN, UK.",
            "firstname": "Hannah",
            "initials": "H",
            "lastname": "Mitchell"
        },
        {
            "affiliation": "UCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.\nResearch Department of Surgical Biotechnology, Division of Surgery and Interventional Science, University College London, London NW3 2PF, UK.\nUCL Institute of Immunity and Transplantation, University College London, London NW3 2PF, UK.",
            "firstname": "Reza",
            "initials": "R",
            "lastname": "Motallebzadeh"
        },
        {
            "affiliation": "Division of Nephrology, Department of Medicine, Washington University in St Louis, St Louis, MO 63110, USA.",
            "firstname": "Yoshiharu",
            "initials": "Y",
            "lastname": "Muto"
        },
        {
            "affiliation": "Central Laser Facility, Science and Technologies Facilities Council, UK Research and Innovation, Didcot OX11 0QX, UK.",
            "firstname": "Robert",
            "initials": "R",
            "lastname": "Lees"
        },
        {
            "affiliation": "Central Laser Facility, Science and Technologies Facilities Council, UK Research and Innovation, Didcot OX11 0QX, UK.",
            "firstname": "Sarah",
            "initials": "S",
            "lastname": "Needham"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.",
            "firstname": "Dale",
            "initials": "D",
            "lastname": "Moulding"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nUCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.",
            "firstname": "Jennie C",
            "initials": "JC",
            "lastname": "Chandler"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nUCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.\nDepartment of Mechanical Engineering, University College London, London WC1E 7JE, UK.",
            "firstname": "Sonal",
            "initials": "S",
            "lastname": "Nandanwar"
        },
        {
            "affiliation": "UCL Centre for Advanced Biomedical Imaging, University College London, London WC1E 6DD, UK.\nDepartment of Mechanical Engineering, University College London, London WC1E 7JE, UK.",
            "firstname": "Claire L",
            "initials": "CL",
            "lastname": "Walsh"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nUCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.",
            "firstname": "Paul J D",
            "initials": "PJD",
            "lastname": "Winyard"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.",
            "firstname": "Peter J",
            "initials": "PJ",
            "lastname": "Scambler"
        },
        {
            "affiliation": "Lymphovascular Medicine and Translational 3D-Histopathology Research Group, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin 10117, Germany.\nBerlin Institute of Health at Charit\u00e9-Universit\u00e4tsmedizin Berlin, BIH Center for Regenerative Therapies, Berlin 10117, Germany.",
            "firstname": "Ren\u00e9",
            "initials": "R",
            "lastname": "H\u00e4gerling"
        },
        {
            "affiliation": "Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge CB2 1TN, UK.\nWellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK.",
            "firstname": "Menna R",
            "initials": "MR",
            "lastname": "Clatworthy"
        },
        {
            "affiliation": "Division of Nephrology, Department of Medicine, Washington University in St Louis, St Louis, MO 63110, USA.",
            "firstname": "Benjamin D",
            "initials": "BD",
            "lastname": "Humphreys"
        },
        {
            "affiliation": "UCL Centre for Advanced Biomedical Imaging, University College London, London WC1E 6DD, UK.",
            "firstname": "Mark F",
            "initials": "MF",
            "lastname": "Lythgoe"
        },
        {
            "affiliation": "UCL Centre for Advanced Biomedical Imaging, University College London, London WC1E 6DD, UK.",
            "firstname": "Simon",
            "initials": "S",
            "lastname": "Walker-Samuel"
        },
        {
            "affiliation": "School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester M13 9PT, UK.",
            "firstname": "Adrian S",
            "initials": "AS",
            "lastname": "Woolf"
        },
        {
            "affiliation": "Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.\nUCL Centre for Kidney and Bladder Health, University College London, London WC1E 6BT, UK.",
            "firstname": "David A",
            "initials": "DA",
            "lastname": "Long"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2025. Published by The Company of Biologists.",
    "doi": "10.1242/dmm.052024",
    "journal": "Disease models & mechanisms",
    "keywords": [
        "Magnetic resonance imaging",
        "Nephrology",
        "Perfusion",
        "Single-cell RNA sequencing",
        "Three-dimensional microscopy",
        "Vasculature"
    ],
    "methods": null,
    "publication_date": "2025-03-21",
    "pubmed_id": "40114603",
    "results": null,
    "title": "Microvascular aberrations found in human polycystic kidneys are an early feature in a Pkd1 mutant mouse model.",
    "xml": "<Element 'PubmedArticle' at 0x788505e51850>"
}