Parallel generation of easily selectable multiple nephronal cell types from human pluripotent stem cells
Summary
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.
| Authors | Hariharan K, Stachelscheid H, Rossbach B, Oh SJ, Mah N, Schmidt-Ott K, Kurtz A, Reinke P |
|---|---|
| Journal | Cellular and molecular life sciences : CMLS |
| Publication Date | 2019 Jan;76(1):179-192 |
| PubMed | 30310934 |
| PubMed Central | PMC11105784 |
| DOI | 10.1007/s00018-018-2929-2 |