{
    "abstract": "Postnatal kidney growth is substantial and involves expansion in kidney tubules without growth of new nephrons, which are the functional units of the kidney. Proliferation and differentiation pathways underpinning nephron elongation are not well defined. To address this, we performed sequential characterization of mouse kidney transcriptomics at the single cell level. Single nuclear RNA sequencing (snRNA-seq) was performed on kidney tissue from male and female mice at 1, 2, 4 and 12 weeks of age using the 10x Chromium platform. Unbiased clustering was performed on 68,775 nuclei from 16 animals. 31 discrete cellular clusters were seen, which were identified through comparison of their gene expression profiles to canonical markers of kidney cell populations. High levels of proliferation were evident at early time points in some cell types, especially tubular cells, but not in other cell types, for example podocytes. Proliferation was especially evident in Proximal Tubular Cells (PTCs) which are the most abundant cell type in the adult kidney. Uniquely when compared to other kidney cell types, PTCs demonstrated sex-specific expression profiles at late, but not early, time points. Mapping of PTC differentiation pathways using techniques including trajectory and RNA Velocity analyses delineated increasing PTC specialization and sex-specific phenotype specification. Our single-cell transcriptomics data characterise cellular states observed during kidney growth. We have identified PTC differentiation pathways that lead to sex-specific tubular cell phenotypes. Tubular proliferative responses are of central importance in postnatal kidney growth and have also been linked to kidney recovery versus fibrosis following injury. Our unbiased and comprehensive dataset of tubular cell development can be used to identify candidate pathways for therapeutic targeting.",
    "authors": [
        {
            "affiliation": "Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.\nWales Kidney Research Unit, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.\nDivision of Nephrology, Kidney Research Center, Linkou Chang Gung Memorial Hospital, Linkou, Taiwan.",
            "firstname": "Yueh-An",
            "initials": "YA",
            "lastname": "Lu"
        },
        {
            "affiliation": "Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.\nWales Kidney Research Unit, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.",
            "firstname": "Tanya",
            "initials": "T",
            "lastname": "Smith"
        },
        {
            "affiliation": "Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.\nWales Kidney Research Unit, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.",
            "firstname": "Sumukh",
            "initials": "S",
            "lastname": "Deshpande"
        },
        {
            "affiliation": "Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei, Taiwan.\nDivision of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, New Taipei, Taiwan.",
            "firstname": "Chia-Te",
            "initials": "CT",
            "lastname": "Liao"
        },
        {
            "affiliation": "Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.\nWales Kidney Research Unit, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.",
            "firstname": "Bnar",
            "initials": "B",
            "lastname": "Talabani"
        },
        {
            "affiliation": "Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.\nWales Kidney Research Unit, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.",
            "firstname": "Irina",
            "initials": "I",
            "lastname": "Grigorieva"
        },
        {
            "affiliation": "Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.\nWales Kidney Research Unit, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.",
            "firstname": "Anna",
            "initials": "A",
            "lastname": "Mason"
        },
        {
            "affiliation": "Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.",
            "firstname": "Robert",
            "initials": "R",
            "lastname": "Andrews"
        },
        {
            "affiliation": "Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.\nWales Kidney Research Unit, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.",
            "firstname": "Timothy",
            "initials": "T",
            "lastname": "Bowen"
        },
        {
            "affiliation": "Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.\nDementia Research Institute at Cardiff University, Cardiff, UK.",
            "firstname": "Philip R",
            "initials": "PR",
            "lastname": "Taylor"
        },
        {
            "affiliation": "Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK. fraserdj@cardiff.ac.uk.\nWales Kidney Research Unit, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK. fraserdj@cardiff.ac.uk.",
            "firstname": "Donald",
            "initials": "D",
            "lastname": "Fraser"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2024. The Author(s).",
    "doi": "10.1038/s41598-024-73102-7",
    "journal": "Scientific reports",
    "keywords": [
        "Cell biology and structure",
        "Chronic kidney disease",
        "Epithelial",
        "Kidney tubule",
        "MRNA",
        "Proximal tubule",
        "Renal epithelial cell",
        "Renal fibrosis",
        "Renal tubular epithelial cells"
    ],
    "methods": null,
    "publication_date": "2024-10-15",
    "pubmed_id": "39402239\n26969971\n30510133\n34155061\n32571916\n30565997\n35529086\n33308019\n36758122\n29846586\n31178118\n29608179\n31948481\n31740819\n30954475\n30089906\n30787437\n8538762\n35931682\n31689386\n36300620\n24780737\n26969971\n29449453\n29870722\n33859189\n29622724\n35821371\n28774999\n36496458\n32662516\n32111728",
    "results": null,
    "title": "Sex-specific proximal tubular cell differentiation pathways identified by single-nucleus RNA sequencing.",
    "xml": "<Element 'PubmedArticle' at 0x7885054e4db0>"
}