title: Dissecting Stages of Human Kidney Development and Tumorigenesis with Surface Markers Affords Simple Prospective Purification of Nephron Stem Cells.
abstract: When assembling a nephron during development a multipotent stem cell pool becomes restricted as differentiation ensues. A faulty differentiation arrest in this process leads to transformation and initiation of a Wilms' tumor. Mapping these transitions with respective surface markers affords accessibility to specific cell subpopulations. NCAM1 and CD133 have been previously suggested to mark human renal progenitor populations. Herein, using cell sorting, RNA sequencing, in vitro studies with serum-free media and in vivo xenotransplantation we demonstrate a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1(+)CD133(-) marks SIX2(+) multipotent renal stem cells transiting to NCAM1(+)CD133(+) differentiating segment-specific SIX2(-) epithelial progenitors and NCAM1(-)CD133(+) differentiated nephron cells. In tumorigenesis, NCAM1(+)CD133(-) marks SIX2(+) blastema that includes the ALDH1(+) WT cancer stem/initiating cells, while NCAM1(+)CD133(+) and NCAM1(-)CD133(+) specifying early and late epithelial differentiation, are severely restricted in tumor initiation capacity and tumor self-renewal. Thus, negative selection for CD133 is required for defining NCAM1(+) nephron stem cells in normal and malignant nephrogenesis.
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer, Israel.|The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Naomi
authors.initials: N
authors.lastname: Pode-Shakked
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Pleniceanu
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Rotem
authors.initials: R
authors.lastname: Gershon
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Shukrun
authors.affiliation: Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Kanter
authors.affiliation: Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Bucris
authors.affiliation: The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer, Israel.|The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Ben
authors.initials: B
authors.lastname: Pode-Shakked
authors.affiliation: Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Tam
authors.affiliation: Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Hadar
authors.initials: H
authors.lastname: Tam
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Revital
authors.initials: R
authors.lastname: Caspi
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|The Maurice and Gabriela Goldschleger Eye Research Institute, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Pri-Chen
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Einav
authors.initials: E
authors.lastname: Vax
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer, Israel.|The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Sheba Medical Center, Tel-Hashomer, Israel.|The Joseph Buchman Gynecology and Maternity Center, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Katz
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Dorit
authors.initials: D
authors.lastname: Omer
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Harari-Steinberg
authors.affiliation: Faculty of Engineering and Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Kalisky
authors.affiliation: Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Tel-Hashomer, Israel.|Division of Pediatric Nephrology, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dekel
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007668:Kidney / Q000196:embryology / Q000378:metabolism*; D008297:Male; D016688:Mice, Inbred NOD; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009399:Nephrons / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D015415:Biomarkers; D019002:CD56 Antigen; D018398:Homeodomain Proteins; C522918:NCAM1 protein, human; D009419:Nerve Tissue Proteins; C484762:SIX2 protein, human