Comparative Analysis and Refinement of Human PSC-Derived Kidney Organoid Differentiation with Single-Cell Transcriptomics. Wu, H., Uchimura, K., Donnelly, E. L., Kirita, Y., Morris, S. A., & Humphreys, B. D. Cell Stem Cell. Paper doi abstract bibtex Kidney organoids derived from human pluripotent stem cells have great utility for investigating organogenesis and disease mechanisms and, potentially, as a replacement tissue source, but how closely organoids derived from current protocols replicate adult human kidney is undefined. We compared two directed differentiation protocols by single-cell transcriptomics of 83,130 cells from 65 organoids with single-cell transcriptomes of fetal and adult kidney cells. Both protocols generate a diverse range of kidney cells with differing ratios, but organoid-derived cell types are immature, and 10%?20% of cells are non-renal. Reconstructing lineage relationships by pseudotemporal ordering identified ligands, receptors, and transcription factor networks associated with fate decisions. Brain-derived neurotrophic factor (BDNF) and its cognate receptor NTRK2 were expressed in the neuronal lineage during organoid differentiation. Inhibiting this pathway improved organoid formation by reducing neurons by 90% without affecting kidney differentiation, highlighting the power of single-cell technologies to characterize and improve organoid differentiation.
@article{wu_comparative_nodate,
title = {Comparative {Analysis} and {Refinement} of {Human} {PSC}-{Derived} {Kidney} {Organoid} {Differentiation} with {Single}-{Cell} {Transcriptomics}},
issn = {1934-5909},
url = {https://doi.org/10.1016/j.stem.2018.10.010},
doi = {10.1016/j.stem.2018.10.010},
abstract = {Kidney organoids derived from human pluripotent stem cells have great utility for investigating organogenesis and disease mechanisms and, potentially, as a replacement tissue source, but how closely organoids derived from current protocols replicate adult human kidney is undefined. We compared two directed differentiation protocols by single-cell transcriptomics of 83,130 cells from 65 organoids with single-cell transcriptomes of fetal and adult kidney cells. Both protocols generate a diverse range of kidney cells with differing ratios, but organoid-derived cell types are immature, and 10\%?20\% of cells are non-renal. Reconstructing lineage relationships by pseudotemporal ordering identified ligands, receptors, and transcription factor networks associated with fate decisions. Brain-derived neurotrophic factor (BDNF) and its cognate receptor NTRK2 were expressed in the neuronal lineage during organoid differentiation. Inhibiting this pathway improved organoid formation by reducing neurons by 90\% without affecting kidney differentiation, highlighting the power of single-cell technologies to characterize and improve organoid differentiation.},
urldate = {2018-11-15},
journal = {Cell Stem Cell},
author = {Wu, Haojia and Uchimura, Kohei and Donnelly, Erinn L. and Kirita, Yuhei and Morris, Samantha A. and Humphreys, Benjamin D.},
}
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Both protocols generate a diverse range of kidney cells with differing ratios, but organoid-derived cell types are immature, and 10%?20% of cells are non-renal. Reconstructing lineage relationships by pseudotemporal ordering identified ligands, receptors, and transcription factor networks associated with fate decisions. Brain-derived neurotrophic factor (BDNF) and its cognate receptor NTRK2 were expressed in the neuronal lineage during organoid differentiation. 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