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Nat Commun. 2019 Nov 29;10(1):5462. doi: 10.1038/s41467-019-13382-0.

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

Author information

1
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
2
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
3
Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
4
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
5
Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
6
Broad Institute of MIT and Harvard, Cambridge, MA, USA. agreka@bwh.harvard.edu.
7
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. agreka@bwh.harvard.edu.

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.

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