title: Wilms' tumor blastemal stem cells dedifferentiate to propagate the tumor bulk.
abstract: An open question remains in cancer stem cell (CSC) biology whether CSCs are by definition at the top of the differentiation hierarchy of the tumor. Wilms' tumor (WT), composed of blastema and differentiated renal elements resembling the nephrogenic zone of the developing kidney, is a valuable model for studying this question because early kidney differentiation is well characterized. WT neural cell adhesion molecule 1-positive (NCAM1(+)) aldehyde dehydrogenase 1-positive (ALDH1(+)) CSCs have been recently isolated and shown to harbor early renal progenitor traits. Herein, by generating pure blastema WT xenografts, composed solely of cells expressing the renal developmental markers SIX2 and NCAM1, we surprisingly show that sorted ALDH1(+) WT CSCs do not correspond to earliest renal stem cells. Rather, gene expression and proteomic comparative analyses disclose a cell type skewed more toward epithelial differentiation than the bulk of the blastema. Thus, WT CSCs are likely to dedifferentiate to propagate WT blastema.
authors: Pediatric Stem Cell Research Institute, Sheba Medical Center, Tel Hashomer 5262000, Israel ; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Ramat-Gan, Tel Hashomer 5262000, Israel ; Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors: Rachel
authors: R
authors: Shukrun
authors: Pediatric Stem Cell Research Institute, Sheba Medical Center, Tel Hashomer 5262000, Israel ; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Ramat-Gan, Tel Hashomer 5262000, Israel ; Dr. Pinchas Borenstein Talpiot Medical Leadership Program 2013, Sheba Medical Center, Tel Hashomer 5262000, Israel ; Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors: Naomi
authors: N
authors: Pode-Shakked
authors: Pediatric Stem Cell Research Institute, Sheba Medical Center, Tel Hashomer 5262000, Israel ; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Ramat-Gan, Tel Hashomer 5262000, Israel ; Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors: Oren
authors: O
authors: Pleniceanu
authors: Pediatric Stem Cell Research Institute, Sheba Medical Center, Tel Hashomer 5262000, Israel ; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Ramat-Gan, Tel Hashomer 5262000, Israel ; Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors: Dorit
authors: D
authors: Omer
authors: Pediatric Stem Cell Research Institute, Sheba Medical Center, Tel Hashomer 5262000, Israel ; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Ramat-Gan, Tel Hashomer 5262000, Israel ; Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors: Einav
authors: E
authors: Vax
authors: Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Ramat-Gan, Tel Hashomer 5262000, Israel ; Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors: Eyal
authors: E
authors: Peer
authors: The Maurice and Gabriela Goldschleger Eye Research Institute, Sheba Medical Center, Tel Hashomer 5262000, Israel.
authors: Sara
authors: S
authors: Pri-Chen
authors: Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Ramat-Gan, Tel Hashomer 5262000, Israel.
authors: Jasmine
authors: J
authors: Jacob
authors: Department of Genetics, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Qianghua
authors: Q
authors: Hu
authors: Pediatric Stem Cell Research Institute, Sheba Medical Center, Tel Hashomer 5262000, Israel ; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Ramat-Gan, Tel Hashomer 5262000, Israel.
authors: Orit
authors: O
authors: Harari-Steinberg
authors: Department of Genetics, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Vicki
authors: V
authors: Huff
authors: Pediatric Stem Cell Research Institute, Sheba Medical Center, Tel Hashomer 5262000, Israel ; Sheba Centers for Regenerative Medicine and Cancer Research, Sheba Medical Center, Ramat-Gan, Tel Hashomer 5262000, Israel ; The Maurice and Gabriela Goldschleger Eye Research Institute, Sheba Medical Center, Tel Hashomer 5262000, Israel ; Division of Pediatric Nephrology, Sheba Medical Center, Tel Hashomer 5262000, Israel ; Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
authors: Benjamin
authors: B
authors: Dekel
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D050697:Retinal Dehydrogenase / Q000378:metabolism; D009396:Wilms Tumor / Q000378:metabolism* / Q000473:pathology*
chemical_list: D019002:CD56 Antigen; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase