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Single cell census of human kidney organoids shows reproducibility and diminished off-target cells after transplantation

Author

Listed:
  • Ayshwarya Subramanian

    (Broad Institute of MIT and Harvard)

  • Eriene-Heidi Sidhom

    (Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital and Harvard Medical School)

  • Maheswarareddy Emani

    (Broad Institute of MIT and Harvard)

  • Katherine Vernon

    (Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital and Harvard Medical School)

  • Nareh Sahakian

    (Broad Institute of MIT and Harvard)

  • Yiming Zhou

    (Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital and Harvard Medical School)

  • Maria Kost-Alimova

    (Broad Institute of MIT and Harvard)

  • Michal Slyper

    (Broad Institute of MIT and Harvard)

  • Julia Waldman

    (Broad Institute of MIT and Harvard)

  • Danielle Dionne

    (Broad Institute of MIT and Harvard)

  • Lan T. Nguyen

    (Broad Institute of MIT and Harvard)

  • Astrid Weins

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Jamie L. Marshall

    (Broad Institute of MIT and Harvard)

  • Orit Rosenblatt-Rosen

    (Broad Institute of MIT and Harvard)

  • Aviv Regev

    (Broad Institute of MIT and Harvard
    Massachusetts Institute of Technology)

  • Anna Greka

    (Broad Institute of MIT and Harvard
    Brigham and Women’s Hospital and Harvard Medical School)

Abstract

Human iPSC-derived kidney organoids have the potential to revolutionize discovery, but assessing their consistency and reproducibility across iPSC lines, and reducing the generation of off-target cells remain an open challenge. Here, we profile four human iPSC lines for a total of 450,118 single cells to show how organoid composition and development are comparable to human fetal and adult kidneys. Although cell classes are largely reproducible across time points, protocols, and replicates, we detect variability in cell proportions between different iPSC lines, largely due to off-target cells. To address this, we analyze organoids transplanted under the mouse kidney capsule and find diminished off-target cells. Our work shows how single cell RNA-seq (scRNA-seq) can score organoids for reproducibility, faithfulness and quality, that kidney organoids derived from different iPSC lines are comparable surrogates for human kidney, and that transplantation enhances their formation by diminishing off-target cells.

Suggested Citation

  • Ayshwarya Subramanian & Eriene-Heidi Sidhom & Maheswarareddy Emani & Katherine Vernon & Nareh Sahakian & Yiming Zhou & Maria Kost-Alimova & Michal Slyper & Julia Waldman & Danielle Dionne & Lan T. Ngu, 2019. "Single cell census of human kidney organoids shows reproducibility and diminished off-target cells after transplantation," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13382-0
    DOI: 10.1038/s41467-019-13382-0
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    Cited by:

    1. Jessica M. Vanslambrouck & Sean B. Wilson & Ker Sin Tan & Ella Groenewegen & Rajeev Rudraraju & Jessica Neil & Kynan T. Lawlor & Sophia Mah & Michelle Scurr & Sara E. Howden & Kanta Subbarao & Melissa, 2022. "Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    2. Moritz Lassé & Jamal El Saghir & Celine C. Berthier & Sean Eddy & Matthew Fischer & Sandra D. Laufer & Dominik Kylies & Arvid Hutzfeldt & Léna Lydie Bonin & Bernhard Dumoulin & Rajasree Menon & Virgin, 2023. "An integrated organoid omics map extends modeling potential of kidney disease," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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