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Single Cell Sequencing and Kidney Organoids Generated from Pluripotent Stem Cells

Wu H, Humphreys BD

Clinical journal of the American Society of Nephrology : CJASN, 2020

Abstract

Methods to differentiate human pluripotent stem cells into kidney organoids were first introduced about 5 years ago, and since that time, the field has grown substantially. Protocols are producing increasingly complex three-dimensional structures, have been used to model human kidney disease, and have been adapted for high-throughput screening. Over this same time frame, technologies for massively parallel, single-cell RNA sequencing (scRNA-seq) have matured. Now, both of these powerful approaches are being combined to better understand how kidney organoids can be applied to the understanding of kidney development and disease. There are several reasons why this is a synergistic combination. Kidney organoids are complicated and contain many different cell types of variable maturity. scRNA-seq is an unbiased technology that can comprehensively categorize cell types, making it ideally suited to catalog all cell types present in organoids. These same characteristics also make scRNA-seq a powerful approach for quantitative comparisons between protocols, batches, and pluripotent cell lines as it becomes clear that reproducibility and quality can vary across all three variables. Lineage trajectories can be reconstructed using scRNA-seq data, enabling the rational adjustment of differentiation strategies to promote maturation of desired kidney cell types or inhibit differentiation of undesired off-target cell types. Here, we review the ways that scRNA-seq has been successfully…

How strong is the evidence?

Evidence Hub reads this as a review, done in cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.

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