GEO DataSets

(Submitter supplied) Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that over-expression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in pathology highly reminiscent of Wilms tumor.

Organism:

Mus musculus

Type:

Expression profiling by array

Dataset:

GDS5415

Platform:

GPL6885

8 Samples

Download data: TXT

Analysis of kidney tumors from Lin28a transgenics at 5 weeks and 4 months of age. Overexpression of heterochronic regulator Lin28 during kidney development promotes Wilms tumor formation. Results provide insight into the role of Lin28 in Wilms tumor formation.

Organism:

Mus musculus

Type:

Expression profiling by array, count, 2 age, 2 disease state sets

Platform:

GPL6885

Series:

GSE56323

8 Samples

Download data

(Submitter supplied) Wilms tumors are pediatric cancers thought to arise from kidney-specific stem cells. In order to identify transcriptional and epigenetic mechanisms that drive these malignant cells, we compared genomewide chromatin profiles of Wilms tumors to embryonic stem (ES) cells and normal kidney.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL9052

12 Samples

Download data: WIG

(Submitter supplied) In this study, we investigated the role of LIN28 in intestinal tumor initiation and invasive progression. We generated animal models with just intestinal LIN28B overexpression, or in combination with Apcmin/+ background. The animals develop intestinal and colorectal tumors with histology ranging from adenoma to adenocarcinoma.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6885

16 Samples

Download data: IDAT, TXT

(Submitter supplied) Lin28A and its paralog Lin28B are RNA binding proteins that regulate gene expression by inhibition of the maturation of the Per/Pri Let-7 miRNAs family and also via Let-7 independent mechanism. To study the effect of Lin28A ectopic-expression on mouse embryonic development we used a transgenic mice strain that combine a Cre-Lox system and a Tet-On system (herein Lox-stop-Lox-TetOn-Lin28A mice) and enable spatial and temporal control of transgenic Lin28A over-expression. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

34 Samples

Download data: XLSX

(Submitter supplied) To characterize the in vivo role of DROSHA mutations during kidney development and their oncogenic potential, we analyzed mouse lines with either a targeted deletion of Drosha or an inducible expression of human DROSHA carrying a tumor-specific E1147K mutation that acts in a dominant negative manner.

Organism:

Mus musculus

Type:

Non-coding RNA profiling by high throughput sequencing

Platform:

GPL23479

9 Samples

Download data: TXT

(Submitter supplied) Purpose: Loss of DIS3L2 in humans is associated with congenital overgrowth in Perlman syndrome, as well as with the development of Wilms tumors. DIS3L2 is an exoribonuclease with a demonstrated preference for 3’-uridylated RNA substrates. However, its targets relevant to human disease are poorly understood. Our goal was to address transcriptomic changes in DIS3L2 deficient mouse nephron progenitor cells, a cell type of the developing kidney with demonstrated relevance to Wilms tumorigenesis. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

5 Samples

Download data: TXT

(Submitter supplied) To study role of Lin28/let-7 axis on nephrogenesis, we profiled kidney transcriptom of LIN28 OE, let-7 KO, and their wild-type littermate control mice.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

12 Samples

Download data: BEDGRAPH, BW, TXT

(Submitter supplied) Comparison of mouse P19 and P19+Lin28 cells at day 5 of retinoic acid-induced differentiation The cell lines differ in that one constitutively expresses Lin28 from a heterologous promoter.

Organism:

human gammaherpesvirus 4; JC polyomavirus; Human gammaherpesvirus 8; Betapolyomavirus macacae; Homo sapiens; Murid gammaherpesvirus 4; Betapolyomavirus hominis; Mus musculus; Human alphaherpesvirus 1; Human betaherpesvirus 5; Murid betaherpesvirus 1; Human immunodeficiency virus 1; Rattus norvegicus

Type:

Non-coding RNA profiling by array

Platform:

GPL7722

4 Samples

Download data: TXT

(Submitter supplied) LIN28 is an RNA-binding protein expressed in many developing tissues. It can block let-7 microRNA processing and help promote pluripotency. We observe LIN28 expression in the developing neural tube, colocalizing with SOX2, suggesting a role in neural development. To better understand its normal developmental function, we investigated LIN28 activity during neurogliogenesis in vitro where the succession of neuronal to glial cell fates occurs as it does in vivo. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL8321

4 Samples

Download data: CEL

(Submitter supplied) Purpose: Bulk transcriptomics analysis of Wilms tumor SIX2+CITED1+ cells to compare and identify unique nephron progenitor transcriptome profiling (RNA-seq) signature between unfavorable and favorable Wilms Tumors and against human fetal kidney Methods: Wilms tumor samples were collected and transported on ice at 4°C in RPMI-1640 and a single cell suspensions were prepared following mechanical and enzymatic dissociation as previously publication. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

3 Samples

Download data: CSV

(Submitter supplied) Purpose: Bulk transcriptomics analysis of Wilms tumor SIX2+CITED1+ cells to compare and identify unique nephron progenitor transcriptome profiling (RNA-seq) signature between unfavorable and favorable Wilms Tumors and against human fetal kidney Methods: Wilms tumor and human fetal kidney samples were collected and transported on ice at 4°C in RPMI-1640 and a single cell suspensions were prepared following mechanical and enzymatic dissociation as previously publication. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

5 Samples

Download data: TXT

(Submitter supplied) Comparative RNA and small RNA sequencing analysis of in vitro differentiated β like cells, in vivo matured β cells, adult islet cells, and Lin28 deficient in vitro differentiated β like cells

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Non-coding RNA profiling by high throughput sequencing

Platform:

GPL11154

24 Samples

Download data: TXT

(Submitter supplied) 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.

Organism:

Homo sapiens

Type:

Non-coding RNA profiling by high throughput sequencing

Platform:

GPL16288

12 Samples

Download data: GFF

(Submitter supplied) Wilms tumors are genetically heterogeneous kidney tumors whose cells of origin are unknown. Tumors with WT1 mutations and concomitant loss of the wild-type allele represent a distinct subgroup, frequently associated with mutations in CTNNB1. Here we describe the establishment and characterization of long-term cell cultures derived from five individual Wilms tumors with WT1 mutations. Three of these tumor cell lines also had CTNNB1 mutations and an activated canonical Wnt signaling pathway as measured by β-catenin/TCF transcriptional activity. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6480

29 Samples

Download data: TXT

(Submitter supplied) Wilms tumor (WT), a childhood kidney cancer with embryonal origins, has been extensively characterised for genetic and epigenetic alterations, but a proportion of WTs still lack identifiable abnormalities.  To uncover DNA methylation changes critical for WT pathogenesis, we compared the epigenome of fetal kidney with two WT cell lines, using methyl-CpG immunoprecipitation.  We filtered our results to remove common cancer-associated epigenetic changes, and to enrich for genes involved in early kidney development.  This identified four candidate genes that were hypermethylated in WT cell lines compared to fetal kidney, of which ESRP2 (epithelial splicing regulatory protein 2), was the most promising gene for further study.  ESRP2 was commonly repressed by DNA methylation early in WT development (in nephrogenic rests) and could be reactivated by DNA methyltransferase inhibition in WT cell lines.  When ESRP2 was expressed in WT cell lines, it acted as an inhibitor of cellular proliferation in vitro and in vivo it suppressed tumor growth of orthotopic xenografts in nude mice.  RNA-seq of the ESRP2-expressing WT cell lines identified several novel splicing targets, in addition to well-characterised targets of ESRP2.  One of these targets, LEF1, is a component of the Wnt signalling pathway that is essential for kidney development and commonly disrupted in WT.  We propose a model in which the Wnt pathway can be disrupted in early kidney development to generate WT, either by genetic abnormalities such as WT1 mutations, or by epigenetic defects, such as ESRP2 methylation. 

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

4 Samples

Download data: XLSX

(Submitter supplied) Wilms tumour (WT), a childhood kidney cancer with embryonal origins, has been extensively characterised for genetic and epigenetic alterations, but a proportion of WTs still lack identifiable abnormalities. To uncover DNA methylation changes critical for WT pathogenesis, we compared the epigenome of fetal kidney with two WT cell lines, using methyl-CpG immunoprecipitation. We filtered our results to remove common cancer-associated epigenetic changes, and to enrich for genes involved in early kidney development. more...

Organism:

Homo sapiens

Type:

Methylation profiling by array

Platform:

GPL28758

3 Samples

Download data: GFF, PAIR