Single cell census of human kidney organoids shows reproducibility and diminished off-target cells after transplantation
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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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Melanoma-like, neuronal-like, and muscle-like cells were found using scRNA-seq of kidney organoids, which were consistent with previous observations using conventional methods in this system.
“melanoma-like, neuronal-like, and muscle-like cells were found using scRNA-seq of kidney organoids,72 which were consistent with previous observations using conventional methods in this system.”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [72]
The Results section on the 49 kidney organoid states reports melanoma-like, neuron-like, and muscle-like cells in single-cell profiles and says these populations had been reported previously. Our copy does not specify that the previous observations used conventional methods, so that detail is unsupported. (LLM, conf=0.85)
Experimental — accuracy not yet measuredRecent studies using scRNA-seq to characterize organoid cultures of other tissue types have also identified abnormal cell populations present in their organoid cultures.
“Recent studies using scRNA-seq to characterize organoid cultures of other tissue types have also identified abnormal cell populations present in their organoid cultures.”
From Single-cell transcriptomics of human-skin-equivalent organoids (2023) · cites this paper as [72]
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Self-citation
- Authors
- Subramanian, A., Sidhom, E.-H., Emani, M., Vernon, K., Sahakian, N., Zhou, Y., Kost-Alimova, M., Slyper, M., Waldman, J., Dionne, D., Nguyen, L. T., Weins, A., Marshall, J. L., Rosenblatt-Rosen, O., Regev, A., & Greka, A.
- Affiliations
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Greka, Anna
- ORCID
- Venue
- Nature Communications
- Published
- 2019-11-29
- Volume
- 10
- Issue
- 1
- Pages
- 5462-5462
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6884507
- OpenAlex
- W2990026706
- Cited by
- 211
- References
- 96
- Citations by year
- 2026: 12 · 2025: 27 · 2024: 36 · 2023: 28 · 2022: 39 · 2021: 44 · 2020: 18 · 2019: 6
- FWCI
- 8.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Nature
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK099465, DK095045)
- the Slim Initiative for Genomic Medicine in the Americas (SIGMA), and an NDSEG fellowship
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Keywords
- kidney organoids, induced pluripotent stem cells, single-cell RNA sequencing, reproducibility, organoid transplantation, kidney capsule transplantation
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Humans, Kidney, Organoids, Transplantation, Heterologous, Reproducibility of Results, Kidney Transplantation, Sequence Analysis, RNA, Gene Expression Regulation, Developmental, Mice, Induced Pluripotent Stem Cells, Single-Cell Analysis
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