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EWS-FLI1-induced osteosarcoma model unveiled a crucial role of impaired osteogenic differentiation on osteosarcoma development [ChIP-seq]

ABSTRACT: EWS-FLI1, a multi-functional fusion oncogene, is exclusively detectable in Ewing sarcomas. However, previous studies reported that a subset of osteosarcomas also harbor EWS-ETS family fusion, suggesting that the fusion gene may be involved in the development of a particular type of osteosarcomas. Here using the doxycycline inducible EWS-FLI1 system, we established an EWS-FLI1-dependent osteosarcoma model from murine bone marrow stromal cells. We revealed that the withdrawal of EWS-FLI1 expression enhances the osteogenic differentiation of sarcoma cells, leading to mature bone formation. Taking advantage of induced pluripotent stem cell (iPSC) technology, we also showed that the sarcoma-derived iPSCs with cancer-related genetic abnormalities exhibited the impaired differentiation program of osteogenic lineage irrespective of the EWS-FLI1 expression. Finally, we demonstrated that EWS-FLI1 contributed to in vitro sarcoma development from the sarcoma-iPSCs after osteogenic differentiation. These findings demonstrated that modulating cellular differentiation is fundamental principle of the EWS-FLI1-induced osteosarcoma development. Furthermore, the in vitro cancer model using sarcoma-iPSCs should provide a novel platform for dissecting relationship between cancer genome and cellular differentiation. Chip-seq in mouse EWS-FLI1-induced osteosarcoma cell lines (SCOS#2 )

ORGANISM(S): Mus musculus

SUBMITTER: Yasuhiro Yamada

PROVIDER: E-GEOD-72897 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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EWS-FLI1-induced osteosarcoma model unveiled a crucial role of impaired osteogenic differentiation on osteosarcoma development [gene expression]

Project description:EWS-FLI1, a multi-functional fusion oncogene, is exclusively detectable in Ewing sarcomas. However, previous studies reported that a subset of osteosarcomas also harbor EWS-ETS family fusion, suggesting that the fusion gene may be involved in the development of a particular type of osteosarcomas. Here using the doxycycline inducible EWS-FLI1 system, we established an EWS-FLI1-dependent osteosarcoma model from murine bone marrow stromal cells. We revealed that the withdrawal of EWS-FLI1 expression enhances the osteogenic differentiation of sarcoma cells, leading to mature bone formation. Taking advantage of induced pluripotent stem cell (iPSC) technology, we also showed that the sarcoma-derived iPSCs with cancer-related genetic abnormalities exhibited the impaired differentiation program of osteogenic lineage irrespective of the EWS-FLI1 expression. Finally, we demonstrated that EWS-FLI1 contributed to in vitro sarcoma development from the sarcoma-iPSCs after osteogenic differentiation. These findings demonstrated that modulating cellular differentiation is fundamental principle of the EWS-FLI1-induced osteosarcoma development. Furthermore, the in vitro cancer model using sarcoma-iPSCs should provide a novel platform for dissecting relationship between cancer genome and cellular differentiation. Microarray in mouse EWS-FLI1-induced osteosarcoma cell lines(SCOS#2 and SCOS#12) and sarcoma(SCOS#2)-derived iPSCs. Total 6 samples were analyzed. We can induce EWS-FLI1 expression by Doxycycline-inducible expression system in SCOS#2 and #12. We investigaed EWS-FLI1 activated genes (Dox ON-High) and EWS-FLI1 repressed genes (Dox OFF-High) in SCOS#2 and #12 sarcoma cell lines. Also, we investigated global gene expression pattern of sarcoma-derived iPSCs (iPSC#2-A1 and #2-B5). A link to this sample file can be found below.

2016-03-01 | E-GEOD-72704 | biostudies-arrayexpress

EWS-FLI1-induced osteosarcoma model unveiled a crucial role of impaired osteogenic differentiation on osteosarcoma development [ChIP-seq]

2016-03-01 | GSE72897 | GEO

EWS-FLI1-induced osteosarcoma model unveiled a crucial role of impaired osteogenic differentiation on osteosarcoma development [gene expression]

2016-03-01 | GSE72704 | GEO

Neo-peptides identification in Ewing sarcoma cell lines using proteomics approach

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2022-05-12 | PXD027309 | Pride

EWS-FLI1-induced osteosarcoma model unveiled a crucial role of impaired osteogenic differentiation on osteosarcoma development

Project description:EWS-FLI1-induced osteosarcoma model unveiled a crucial role of impaired osteogenic differentiation on osteosarcoma development

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The human Ewing's Sarcoma oncoprotein EWS-FLI1 causes developmental defects in zebrafish embryos

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A functional liaison between E2F and the aberrant ETS oncogene EWS/FLI1 in Ewing's sarcoma

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