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Stem Cell Reports. 2017 Jul 11;9(1):279-291. doi: 10.1016/j.stemcr.2017.04.026. Epub 2017 May 25.

Evidence of In Vitro Preservation of Human Nephrogenesis at the Single-Cell Level.

Author information

1
Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 52621, Israel; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer 52621, Israel; The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer 52621, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel.
2
Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 52621, Israel; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer 52621, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel.
3
Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan 5290002, Israel.
4
Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 52621, Israel; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer 52621, Israel.
5
Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 52621, Israel; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer 52621, Israel; The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer 52621, Israel; The Joseph Buchman Gynecology and Maternity Center, Sheba Medical Center, Tel-Hashomer 52621, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel.
6
Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 52621, Israel; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer 52621, Israel; Division of Pediatric Nephrology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer 52621, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel. Electronic address: binyamin.dekel@sheba.health.gov.il.

Abstract

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.

KEYWORDS:

Wilms' tumor; cancer stem cells; kidney stem/progenitor cells; renal development; single cell gene expression analysis; stem cell markers; stem cells

PMID:
28552604
PMCID:
PMC5511042
DOI:
10.1016/j.stemcr.2017.04.026
[Indexed for MEDLINE]
Free PMC Article

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