TY - JOUR
T1 - Wilms' tumor blastemal stem cells dedifferentiate to propagate the tumor bulk
AU - Shukrun, Rachel
AU - Pode-Shakked, Naomi
AU - Pleniceanu, Oren
AU - Omer, Dorit
AU - Vax, Einav
AU - Peer, Eyal
AU - Pri-Chen, Sara
AU - Jacob, Jasmine
AU - Hu, Qianghua
AU - Harari-Steinberg, Orit
AU - Huff, Vicki
AU - Dekel, Benjamin
N1 - Funding Information:
We thank Itamar Goldstein for his assistance with the FACS experiments, Peter Hohenstein for critically reading the manuscript, and Yaacov Lawrence for assisting with the ionizing radiation experiments. This work was supported by the MD Anderson Global Academic Programs (to B.D. and V.H.), The Zeiring Foundation, and The Israel Cancer Fund (Grant number PG-11-3072 to B.D.). This work is part of the requirements toward a PhD degree at the Sackler School of Medicine, Tel Aviv University (for R.S.).
PY - 2014/7/8
Y1 - 2014/7/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.stemcr.2014.05.013
DO - 10.1016/j.stemcr.2014.05.013
M3 - Article
C2 - 25068119
AN - SCOPUS:84904263575
SN - 2213-6711
VL - 3
SP - 24
EP - 33
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 1
ER -