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Author Spotlight: Integrating Organoid Models with Single-Cell and Spatial Transcriptomics Technologies
Published on: March 29, 2024
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Comparative Analysis and Refinement of Human PSC-Derived Kidney Organoid Differentiation with Single-Cell
Haojia Wu1, Kohei Uchimura1, Erinn L Donnelly1
1Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Cell Stem Cell
|November 20, 2018
Summary
Human pluripotent stem cell-derived kidney organoids offer research potential but don't fully replicate adult kidneys. Targeting the BDNF pathway improves organoid development by reducing non-renal cells.
Area of Science:
- Stem cell biology
- Developmental biology
- Regenerative medicine
Background:
- Human pluripotent stem cells (hPSCs) are used to generate kidney organoids for studying kidney development and disease.
- Current kidney organoid differentiation protocols' ability to mimic adult human kidney structure and function remains unclear.
Purpose of the Study:
- To compare two directed differentiation protocols for generating kidney organoids from hPSCs.
- To assess the maturity and purity of kidney organoid-derived cells using single-cell transcriptomics.
- To identify molecular pathways regulating kidney organoid development and identify strategies for improvement.
Main Methods:
- Single-cell transcriptomic analysis of 83,130 cells from 65 kidney organoids.
- Comparison with single-cell transcriptomes from fetal and adult human kidney cells.
- Pseudotemporal ordering to reconstruct lineage relationships and identify key regulatory networks.
Main Results:
- Both protocols yielded diverse kidney cell types, but cells were immature and 10-20% were non-renal.
- Identification of brain-derived neurotrophic factor (BDNF) and its receptor NTRK2 in the neuronal lineage.
- Inhibition of the BDNF pathway reduced neuronal contamination by 90% without compromising kidney cell differentiation.
Conclusions:
- Kidney organoids generated by current protocols contain immature and non-renal cells, limiting their fidelity to adult human kidneys.
- Single-cell technologies are powerful tools for characterizing and optimizing organoid differentiation protocols.
- Targeting specific signaling pathways, like BDNF, can significantly improve the purity and developmental efficiency of kidney organoids.
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