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Prospective isolation and characterization of renal cancer stem cells from human Wilms' tumor xenografts leads to tumor eradication

ABSTRACT: Downregulation of specific microRNAs contribute to epithelial-mesenchymal transition of Wilms' tumor cancer initiating cells. In order to gain insight into the biology of initiating cells/cancer stem cells (CIC/CSCs) in Wilms' tumor, we compared the microRNA expression profile of un-sorted propagatable WT xenografts (p-WT Xn), p-WT NCAM+ALDH1+-derived Xn and human fetal kidneys (hFKs). Global microRNA expression analysis showed specific microRNAs to differentially express identifying a strong miRNA signature for the NCAM+ALDH1+ WT CICs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33332 | GEO | 2012/12/01

SECONDARY ACCESSION(S): PRJNA148957

REPOSITORIES: GEO

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Prospective isolation and characterization of renal cancer stem cells from human Wilms' tumor xenografts leads to tumor eradication

Project description:Downregulation of specific microRNAs contribute to epithelial-mesenchymal transition of Wilms' tumor cancer initiating cells. In order to gain insight into the biology of initiating cells/cancer stem cells (CIC/CSCs) in Wilms' tumor, we compared the microRNA expression profile of un-sorted propagatable WT xenografts (p-WT Xn), p-WT NCAM+ALDH1+-derived Xn and human fetal kidneys (hFKs). Global microRNA expression analysis showed specific microRNAs to differentially express identifying a strong miRNA signature for the NCAM+ALDH1+ WT CICs. 3 different tissue types (described in 'summary') each with n=4 were homoginized and analyzed for their global miRNA expression profiles. Human Fetal Kidney tissues were used as a control.

2012-12-01 | E-GEOD-33332 | biostudies-arrayexpress

Dissecting stages of human kidney development and Tumorigenesis with surface markers affords simple prospective Purification of nephron stem cells

Project description: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. Human fetal kidney mRNA profiles of 3 cell populations (NCAM1+/CD133-, NCAM+/CD133+, NCAM-/CD133+) were generated by deep sequencing using Illumina HiSeq.

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The Wilms' tumor blastema propagating cell is a self-renewing committed epithelial stem cell

Project description:Recently the cancer stem cell (CSC) model has been put forward to describe how a subset of cells within the tumor is responsible for tumor growth and heterogeneity. Wilms' tumor (WT), the most common pediatric renal malignancy, arises from developmentally arrested early renal progenitors. WT NCAM1+ALDH1+ CSCs have been recently isolated and shown to localize to tumor blastema. Herein by generating 'blastema'-only WT xenografts composed solely by cells expressing the SIX2 and NCAM1 embryonic renal stem cell markers, we surprisingly show that sorted ALDH1+ WT CSCs are phenotypically not the earliest renal stem cells. Rather, gene expression and proteomic comparative analysis disclose a more differentiated self-renewing epithelial cell type than bulk of the blastema. Thus, WT CSCs do not represent the transformed counterpart of the most primitive renal stem cell being more differentiated than the presumable WT cell of origin and are likely to de-differentiate to propagate the tumor blastema. We used Wilms tumor Xns, as well as, fetal renal tissue originally obtained from a patients or aborted fetus

2015-12-31 | E-GEOD-57269 | biostudies-arrayexpress

The Wilms' tumor blastema propagating cell is a self-renewing committed epithelial stem cell

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Global mapping of binding sites of Nrf2 in SAS and SAS sphere cells

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2020-03-01 | GSE95818 | GEO

The mRNA levels of CD133 positive and CD133 negative cells after radiation exposure

Project description:The cancer initiating cells (CICs) act as a tumor initiation source. Recent studies have shown that CICs contribute to chemoresistance and radioresistance. The aims of this study were to investigate the relationship of CD133+ liver CICs and radiation resistance and to define a possible mechanism for radioresistance in hepatocellular carcinoma (HCC).

2013-07-20 | GSE22247 | GEO

Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis in Wilms tumors

Project description:Through whole-exome sequencing we identified somatic missense mutations in DICER1 and DROSHA in Wilms tumor, a childhood kidney cancer. DICER1 and DROSHA are key enzymes in the microRNA biogenesis pathway. To determine the effect of these mutations on microRNA expression, we prepared small RNAs from Wilms tumors and used next-generation sequencing to determine the expression levels of microRNAs in the tumors.

2015-04-21 | GSE56955 | GEO

The mRNA levels of CD133 positive and CD133 negative cells after radiation exposure

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Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis in Wilms tumors

2015-04-21 | E-GEOD-56955 | biostudies-arrayexpress

CD109 expression regulates the phenotype of cancer stem-like cells or cancer-initiating cells in epithelioid sarcoma with possible impact on clinical prognosis

Project description:Several human cancers contain a small subpopulation of cells called cancer stem-like cells (CSCs)/cancer initiating cells (CICs), which are defined by the ability of self- renewal, multi-differentiation potential, and tumorigenesis. In current study, we focused on epithelioid sarcoma, which is very rare caner, and isolated CSCs/CICs from epitheloid sarcoma cell line ESX based on ALDH activity using ALDEFLUOR assay towards identification of a new CIC/CSC marker. We performed gene profiling between ALDHhigh and ALDH low cells using cDNA microarray for the identification of good markers of CSCs/CICs of epithelioid sarcoma.

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