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Related Experiment Video

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Optimization of Renal Organoid and Organotypic Culture for Vascularization, Extended Development, and Improved Microscopy Imaging
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Stepwise developmental mimicry generates proximal-biased kidney organoids.

Jack Schnell, Zhen Miao, MaryAnne Achieng

    Biorxiv : the Preprint Server for Biology
    |July 15, 2024
    PubMed
    Summary

    Researchers developed "proximal-biased" kidney organoids to better model kidney development and injury. This advance improves understanding of proximal tubule function and disease, aiding in the development of new therapies for kidney conditions.

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    Area of Science:

    • Nephrology
    • Developmental Biology
    • Stem Cell Biology

    Background:

    • Kidney proximal tubule cells are vital for homeostasis but susceptible to damage.
    • Current human pluripotent stem cell-derived kidney organoids show incomplete proximal tubule development.
    • Modeling proximal tubule injury and disease requires improved organoid systems.

    Purpose of the Study:

    • To engineer kidney organoids with enhanced proximal tubule precursor development.
    • To establish a functional model for studying kidney proximal tubule injury and disease mechanisms.

    Main Methods:

    • Transient manipulation of the PI3K signaling pathway to activate Notch signaling.
    • Utilizing a blueprint of human nephrogenesis for organoid differentiation.
    • Single-cell transcriptional analysis to confirm developmental pathways.

    Main Results:

    • Proximal-biased (PB) organoids successfully generated proximal nephron precursor cells.
    • PB organoids exhibited functional maturity with dextran and albumin uptake.
    • PB organoids showed sensitivity to nephrotoxic agents, mimicking kidney injury responses.

    Conclusions:

    • Transient Notch signaling activation is crucial for proximal nephron development in organoids.
    • PB organoids serve as a relevant model for studying nephron injury mechanisms.
    • This model enhances the utility of kidney organoids for research and therapeutic development.