Molecularly distinct models of zebrafish Myc-induced B cell leukemia
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE119173 | GEO | 2019/08/18
REPOSITORIES: GEO
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Project description:Molecularly distinct models of zebrafish Myc-induced B cell leukemia
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2018-08-06 | GSE109437 | GEO
Project description:A major cause of human deafness and vestibular dysfunction is permanent loss of the mechanosensory hair cells of the inner ear. In non-mammalian vertebrates such as zebrafish, regeneration of missing hair cells can occur throughout life. While a comparative approach has the potential to reveal the basis of such differential regenerative ability, the degree to which the inner ears of fish and mammals share common hair and supporting cell types remains unresolved. Here we perform single-cell RNA sequencing of the zebrafish inner ear at embryonic through adult stages to catalog the diversity of hair and non-sensory supporting cells. We identify a putative progenitor population for hair and supporting cells, as well as distinct hair and supporting cell types in the maculae versus cristae. The hair and supporting cell types differ from those described for the lateral line, a distributed mechanosensory organ in zebrafish in which most studies of hair cell regeneration have been conducted. In the maculae, we identify two subtypes of hair cells that share gene expression with mammalian striolar or extrastriolar hair cells. In situ hybridization reveals that these hair cell subtypes occupy distinct spatial domains within the two major macular organs, the utricle and saccule, consistent with the reported distinct electrophysiological properties of hair cells within these domains. These findings suggest that primitive specialization of spatially distinct striolar and extrastriolar hair cells likely arose in the last common ancestor of fish and mammals. The similarities of inner ear cell type composition between fish and mammals also support using zebrafish as a relevant model for understanding inner ear-specific hair cell function and regeneration.
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Project description:Rhabdomyosarcoma is a pediatric malignancy thought to arise from the uncontrolled proliferation of myogenic cells. Here, we have generated models of rhabdomyosarcoma in the zebrafish by inducing oncogenic KRASG12D expression at different stages during muscle development. Several zebrafish promoters were used including the cdh15 and rag2 promoters that drive gene expression in early muscle progenitors, and the mylz2 promoter that expresses in differentiating myoblasts. The tumors that developed differed in their ability to recapitulate normal myogenesis. cdh15:KRASG12D and rag2:KRASG12D fish developed tumors that displayed an inability to fully undergo muscle differentiation by histologic appearance and gene expression analyses. In contrast, mylz2:KRASG12D tumors more closely resembled mature skeletal muscle and were most similar to well-differentiated human rhabdomyosarcoma by gene expression. mylz2:KRASG12D fish showed significantly improved survival compared to cdh15:KRASG12D and rag2:KRASG12D fish. Tumor-propagating activity was enriched in myf5-expressing cell populations within all of the tumor types. Our results demonstrate that oncogene expression at different stages during muscle development has profound effects on the ability of tumor cells to recapitulate normal myogenesis, altering the tumorigenic capability of these cells. 32 samples total: 7 WT muscle, 9 mylz2-KRAS, 9 cdh15-KRAS, and 7 rag2-KRAS tumors
2013-07-17 | E-GEOD-39731 | biostudies-arrayexpress
Project description:To study the characteristics and mechanisms of Myc-induced zebrafish liver tumor, next-generation sequencing-based SAGE analyses were used to examine the transcriptomes of tumor and control samples. The results indicated that ribosome proteins were overwhelmingly up-regulated in the Myc-induced liver tumors. Cross-species analyses showed that the zebrafish Myc model correlated well with Myc transgenic mouse models for liver cancers. The Myc-induced zebrafish liver tumors also possessed molecular signatures highly similar to human hepatocellular carcinoma (HCC). Thus, our zebrafish model demonstrated the conserved role of Myc in promoting hepatocarcinogenesis in all vertebrate species. Transcriptome profiling of tumor samples (M+D+) and control samples (M-D-, M+D-, M-D+) were generated by deep sequencing, each in duplicates, using 3' RNA-SAGE on the SOLiD system.
2013-04-02 | E-GEOD-40745 | biostudies-arrayexpress
Project description:To study the characteristics and mechanisms of Myc-induced zebrafish liver tumor, next-generation sequencing-based SAGE analyses were used to examine the transcriptomes of tumor and control samples. The results indicated that ribosome proteins were overwhelmingly up-regulated in the Myc-induced liver tumors. Cross-species analyses showed that the zebrafish Myc model correlated well with Myc transgenic mouse models for liver cancers. The Myc-induced zebrafish liver tumors also possessed molecular signatures highly similar to human hepatocellular carcinoma (HCC). Thus, our zebrafish model demonstrated the conserved role of Myc in promoting hepatocarcinogenesis in all vertebrate species.
2013-04-02 | GSE40745 | GEO
Project description:Rhabdomyosarcoma is a pediatric malignancy thought to arise from the uncontrolled proliferation of myogenic cells. Here, we have generated models of rhabdomyosarcoma in the zebrafish by inducing oncogenic KRASG12D expression at different stages during muscle development. Several zebrafish promoters were used including the cdh15 and rag2 promoters that drive gene expression in early muscle progenitors, and the mylz2 promoter that expresses in differentiating myoblasts. The tumors that developed differed in their ability to recapitulate normal myogenesis. cdh15:KRASG12D and rag2:KRASG12D fish developed tumors that displayed an inability to fully undergo muscle differentiation by histologic appearance and gene expression analyses. In contrast, mylz2:KRASG12D tumors more closely resembled mature skeletal muscle and were most similar to well-differentiated human rhabdomyosarcoma by gene expression. mylz2:KRASG12D fish showed significantly improved survival compared to cdh15:KRASG12D and rag2:KRASG12D fish. Tumor-propagating activity was enriched in myf5-expressing cell populations within all of the tumor types. Our results demonstrate that oncogene expression at different stages during muscle development has profound effects on the ability of tumor cells to recapitulate normal myogenesis, altering the tumorigenic capability of these cells.
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