Human pluripotent stem cells (hPSCs) provide a source for the generation of defined kidney cells and renal organoids applicable in regenerative medicine, disease modeling, and drug screening. These applications require the provision of hPSC-derived renal cells by reproducible, scalable, and efficient methods. We established a chemically defined protocol by application of Activin A, BMP4, and Retinoic acid followed by GDNF, which steered hPSCs to the renal lineage and resulted in populations of SIX2+/CITED1+ metanephric mesenchyme- (MM) and of HOXB7+/GRHL2+ ureteric bud (UB)-like cells already by 6 days. Transcriptome analysis corroborated that the PSC-derived cell types at day 8 resemble their renal vesicle and ureteric epithelial counterpart in vivo, forming tubular and glomerular renal cells 6 days later. We demonstrate that starting from hPSCs, our in vitro protocol generates a pool of nephrogenic progenitors at the renal vesicle stage, which can be further directed into specialized nephronal cell types including mesangial-, proximal tubular-, distal tubular, collecting duct epithelial cells, and podocyte precursors after 14 days. This simple and rapid method to produce renal cells from a common precursor pool in 2D culture provides the basis for scaled-up production of tailored renal cell types, which are applicable for drug testing or cell-based regenerative therapies.
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This work was supported by Berlin-Brandenburg School for Regenerative Therapies and the German Federal Ministry of Education and Research (VIP, FKZ 03V0396) and (FKZ 031A303B).
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The authors declare that they have no competing interests.
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Hariharan, K., Stachelscheid, H., Rossbach, B. et al. Parallel generation of easily selectable multiple nephronal cell types from human pluripotent stem cells. Cell. Mol. Life Sci. 76, 179–192 (2019). https://doi.org/10.1007/s00018-018-2929-2
- Renal progenitors
- Renal vesicle