During nephrogenesis, stem/progenitor cells differentiate and give rise to early nephron structures that segment to proximal and distal nephron cell types. Previously, we prospectively isolated progenitors from human fetal kidney (hFK) utilizing a combination of surface markers. However, upon culture nephron progenitors differentiated and could not be robustly maintained in vitro. Here, by culturing hFK in a modified medium used for in vitro growth of mouse nephron progenitors, and by dissection of NCAM+/CD133− progenitor cells according to EpCAM expression (NCAM+/CD133−/EpCAM−, NCAM+/CD133−/EpCAMdim, NCAM+/CD133−/EpCAMbright), we show at single-cell resolution a preservation of uninduced and induced cap mesenchyme as well as a transitioning mesenchymal-epithelial state. Concomitantly, differentiating and differentiated epithelial lineages are also maintained. In vitro expansion of discrete stages of early human nephrogenesis in nephron stem cell cultures may be used for drug screening on a full repertoire of developing kidney cells and for prospective isolation of mesenchymal or epithelial renal lineages for regenerative medicine.
|Number of pages||13|
|Journal||Stem Cell Reports|
|State||Published - 11 Jul 2017|
Bibliographical noteFunding Information:
We wish to thank Jordan Kreidberg, Joseph V. Bonventre, Robert H. Singer, John S. Condeelis, Achia Urbach, Tali H. Bar-Lev, Nissim Ben-Haim, and all members of our labs for fruitful discussions and suggestions. This work was supported by the ICRF (grant nos. 15731 and 15450), the Israel Cancer Association (grant no. 20150916), and The Ziering Foundation (grant no. 45124) (B. D.). T.K., G.T., I.K., and S.O. are supported by the Israel Science Foundation (ICORE no. 1902/12 and grant nos. 1634/13 and 2017/13), the Israel Cancer Association (grant no. 20150911), the Israel Ministry of Health (grant no. 3-10146), and the EU-FP7 (Marie Curie International Reintegration grant no. 618592).
© 2017 The Author(s)
- Wilms’ tumor
- cancer stem cells
- kidney stem/progenitor cells
- renal development
- single cell gene expression analysis
- stem cell markers
- stem cells