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Related Concept Videos

Reporter Genes02:11

Reporter Genes

Reporter genes are a type of protein-coding gene that are often tagged to a gene of interest. Once inside a target cell, reporter genes usually produce visually identifiable characteristics like fluorescence and luminescence when expressed along with the gene of interest. Thus, reporter genes “report” the presence or absence of genes of interest in an organism, determine the gene expression pattern, or track the physical location of a DNA segment or protein in the cell.
Commonly used reporter...

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Dynamic Single Cell Transcriptomics Defines Kidney FGF23/KL Bioactivity and Novel Segment-Specific Inflammatory

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    Fibroblast growth factor 23 (FGF23) regulates phosphate metabolism via its coreceptor, αKlotho (KL). This study reveals FGF23

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    Area of Science:

    • Molecular Endocrinology
    • Renal Physiology
    • Systems Biology

    Background:

    • Fibroblast growth factor 23 (FGF23) and its coreceptor αKlotho (KL) are critical regulators of phosphate metabolism.
    • The precise spatial-temporal mechanisms of renal FGF23 action and its interaction with inflammation remain poorly understood.
    • Altered FGF23 levels are implicated in rare and common metabolic syndromes, highlighting the need to understand its renal functions.

    Purpose of the Study:

    • To elucidate the spatial-temporal mechanisms of FGF23 bioactivity in the kidney at single-cell resolution.
    • To identify specific cell populations and signaling pathways mediating FGF23's effects on phosphate metabolism.
    • To investigate the interplay between FGF23 signaling and inflammatory pathways, particularly TNF/NF-κB.

    Main Methods:

    • Single-cell RNA sequencing (scRNAseq) of mouse kidneys following recombinant FGF23 (rFGF23) injection at multiple time points.
    • Computational analysis of scRNAseq data to identify distinct cell clusters and track FGF23 bioactivity.
    • Integration of ATAC-seq and RNA-seq data to pinpoint genomic regulatory elements involved in FGF23 signaling.

    Main Results:

    • FGF23 bioactivity was mapped to specific renal cell populations, including proximal and distal tubules, dependent on constitutive KL expression.
    • Temporal FGF23 responses induced distinct cellular identities and modulated MAPK and vitamin D metabolic pathways via early and late transcriptional regulons.
    • An unexpected crosstalk between FGF23-mediated MAPK signaling and TNF receptor/NF-κB inflammatory pathways was identified, which inhibited FGF23 bioactivity.

    Conclusions:

    • Novel FGF23-regulated pathways and cellular responses in the kidney have been uncovered at single-cell resolution.
    • The findings reveal a critical interplay between FGF23 signaling and inflammatory pathways (TNF/NF-κB), impacting FGF23 bioactivity.
    • These insights provide a foundation for understanding FGF23-dependent disease mechanisms and developing targeted therapeutic strategies for mineral metabolism disorders.