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Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma

ABSTRACT: Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma

PROVIDER: PRJNA206090 | ENA |

REPOSITORIES: ENA

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Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma (methylation)

Project description:Therapeutic targeting of the Wnt pathway is of high clinical interest for treating bone loss disorders such as osteoporosis. These therapies inhibit the action of negative regulators of osteoblastic Wnt signaling. The observation that Wnt inhibitory factor 1 (WNT1) was epigenetic silencing in osteosarcoma (OS) raised concerns for such a treatment approach. In this study, genome-wide methylation profiling of OS derived from mouse models demonstrated Wif1 silencing in OS is not driven by DNA methylation. Treatment of mouse and human OS cells with methylation and HDAC inhibitors showed Wif1 was unresponsive to methylation inhibition but responded robustly to HDAC inhibition. Consistent with an HDAC dependent mechanism of silencing, the Wif1 locus in OS was characterized by low levels of acetylation and a bivalent H3K4/H3K27 trimethylation state. Wif1 expression marked late stages of normal osteoblast development and stratified OS tumours based on differentiation stage across species. Culture of human and mouse OS cells under differentiation inductive conditions increased expression of Wif1 in parallel with known osteoblast differentiation markers. Together these results demonstrate that Wif1 is not targeted for silencing by DNA methylation in OS. The reduced expression of Wif1 in OS cells is in context with their stage in differentiation. 3 cell lines derived from primary tumors from p53 Rb Osterix-Cre:lox OS model, 3 Osteoblasts (differentiated Kusa4b10 cells (21 days under osteoblastic differentiation conditions)

2015-07-01 | E-GEOD-47571 | biostudies-arrayexpress

Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma (methylation)

2015-07-01 | GSE47571 | GEO

Wnt inhibitory factor 1 (WIF1) is not silenced by DNA methylation in osteosarcoma, and instead, represents a marker of osteoblastic differentiation stage (gene expression)

Project description:The aim was to identify pathways and genes that are transcriptionally deregulated in osteosarcoma due to changes in CpG island DNA methylation. In order to identify candidates, we compared low passage cell cultures derived from a mouse model of osteosarcoma to mature osteoblasts derived by in vitro differentiation of the mouse bone marrow stromal cell line, Kusa4b10. Under cell culture osteoblastic differentiating conditions, Kusa4b10 cells acquire a mature osteoblastic phenotype (21 days). A potential role for DNA methylation in directing gene expression changes was established by integrating gene expression data with genome wide DNA methylation maps generated by methyl-DNA binding domain capture and NimbleGen promoter arrays (MBDCap-Chip).

2015-07-01 | GSE46929 | GEO

Wnt inhibitory factor 1 (WIF1) is not silenced by DNA methylation in osteosarcoma, and instead, represents a marker of osteoblastic differentiation stage (gene expression)

2015-07-01 | E-GEOD-46929 | biostudies-arrayexpress

Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma

Project description:Purpose: We have used microarrays to identify gene expression profiles that distinguish mouse OS cells from normal pre-osteoblast cells and mature osteoblast cells. Methods: Transcriptional profiles of three cell lines derived from tumors from Osx-Cre p53fl/fl Rbfl/fl (fibroblastic OS) mouse model, and from pre-osteoblast cells (Kusa4b10 mouse bone marrow stromal cell line) and osteoblast cells (derived by in vitro differentiation of the Kusab410 mouse bone marrow stromal cell line) were generated by microarray analysis, each in triplicate, using Affymetrix mouse Gene1.0ST arrays. Transcriptional profiles were analyzed in cell lines derived from tumors from a genetically engineered mouse model of human osteosarcoma (Osx-Cre p53fl/fl Rbfl/fl) and osteoblast cells derived from the Kusa4b10 mouse bone marrow stromal cell line, in the undifferentiated state (pre-osteoblasts) and differentiated state (osteoblasts).

2015-01-29 | E-GEOD-63939 | biostudies-arrayexpress

Mus musculus

Project description:Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma

| PRJNA269570 | ENA

Mus musculus

Project description:Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma (methylation)

| PRJNA206096 | ENA

Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma

2015-01-29 | GSE63939 | GEO

Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage and is not silenced by DNA methylation in osteosarcoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-07-01 | GSE47572 | GEO

Mus musculus

Project description:Wnt inhibitory factor 1 (WIF1) is not silenced by DNA methylation in osteosarcoma, and instead, represents a marker of osteoblastic differentiation stage (gene expression)

| PRJNA203105 | ENA

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