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

Ayshwarya Subramanian, Eriene-Heidi Sidhom, Maheswarareddy Emani, Katherine Vernon, Nareh Sahakian, Yiming Zhou, Maria Kost-Alimova, Michal Slyper, Julia Waldman, Danielle Dionne, Lan T. Nguyen, Astrid Weins, Jamie L. Marshall, Orit Rosenblatt-Rosen, Aviv Regev and Anna Greka ()
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Ayshwarya Subramanian: Broad Institute of MIT and Harvard
Eriene-Heidi Sidhom: Broad Institute of MIT and Harvard
Maheswarareddy Emani: Broad Institute of MIT and Harvard
Katherine Vernon: Broad Institute of MIT and Harvard
Nareh Sahakian: Broad Institute of MIT and Harvard
Yiming Zhou: Broad Institute of MIT and Harvard
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
Anna Greka: Broad Institute of MIT and Harvard

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13382-0

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