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A single-cell/nucleus atlas of pediatric rhabdomyosarcoma

ABSTRACT: Rhabdomyosarcoma (RMS) is the most soft tissue sarcoma of childhood and histologically mimics developing skeletal muscle. To better understand RMS, we performed single-cell RNA-seq of one embryonal subtype RMS (ERMS) and one alveolar subtype RMS (ARMS). We expanded our observations by performing single-nucleus RNA-seq of 18 patient tumors (12 ERMS, 6 ARMS). All 18 of these tumors were used to generate orthotopic patient-derived xenografts, and we performed single-cell RNA-seq of all 18 O-PDXs to compare heterogeneity between the original tumor and the patient-derived model. 15 of the O-PDXs underwent lentiviral barcoding, and lineage could be tracked using a separate dial-out PCR step during the single-cell RNA-seq workflow. We performed single-cell RNA-seq of an ex vivo organoid, showing that we can preserve heterogeneity in this model. We expanded our study to the epigenetic level by using single-cell ATAC-sequencing of 7 O-PDXs. Finally, we longitudinally tracked shifts in heterogeneity in an O-PDX model treated with chemotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE174376 | GEO | 2022/04/06

REPOSITORIES: GEO

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Affymetrix SNP array data for pediatric rhabdomyosarcoma (RMS)

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Affymetrix SNP array data for pediatric rhabdomyosarcoma (RMS)

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microRNA-27a contributes to rhabdomyosarcoma cell proliferation through suppression of RARA and RXRA

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Proteomic profiling of rhabdomyosarcoma-derived exosomes yield functional role for extracellular vesicles

Project description:In this study, we interrogated the protein composition of exosomes purified from cell culture supernatants of 5 different RMS cell lines, by LC-MS/MS technology and analysis using bio-informatics tools. We attempted to characterize the differences and similarities between exosomes derived from ERMS and ARMS cells, and common as well as unique characteristics of RMS exosome protein content when compared to that of other cancer and non-cancer cells. Our results identify potential protein exosome biomarkers for RMS to be further investigated in future clinical studies.

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circ-ZNF609 regulates G1-S progression in Rhabdomyosarcoma

Project description:Circular RNAs (circRNAs) represent a class of covalently closed RNAs, derived from a non-canonical splicing event, ubiquitously expressed among Eukaryotes and conserved among different species. We identified a circRNA (circ-ZNF609) involved in the regulation of human primary myoblast proliferation. Upon its depletion, the percentage of proliferating myoblasts was highly reduced. To deepen our knowledge about circ-ZNF609 role in cell cycle regulation, we studied its expression and function in Rhabdomyosarcoma (RMS), a pediatric skeletal muscle malignancy. We found that circ-ZNF609 is up-regulated in biopsies from both the two major RMS subtypes, the alveolar (ARMS) and the embryonal (ERMS), and we discovered that its knock-down blocks proliferation of an ERMS-derived cell line, while it has no effect on ARMS-derived cells. To understand the mechanism through which circ-ZNF609 affects cell proliferation we compared the different effects of circ-ZNF609 depletion in ERMS and ARMS and we identified genes and pathways on which the circRNA acts.

2018-12-14 | GSE117609 | GEO

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Project description:Rhabdomyosarcoma (RMS) is a highly malignant tumour accounting for nearly half of soft tissue sarcomas in children. Altered miRNA levels have been reported in human cancers, including RMS. Using deep sequencing technology, a total of 685 miRNAs were investigated in a group of alveolar RMSs (ARMSs), embryonal RMSs (ERMSs) as well as in normal skeletal muscle (NSM). Bioinformatics pipelines were used for miRNA target prediction and clustering analysis. Ninety-seven miRNAs were significantly deregulated in ARMS and ERMS when compared to NSM. MiR-378 family members were dramatically decreased in RMS tumour tissue and cell lines. Interestingly, members of the miR-378 family presented as a possible target the insulin-like growth factor receptor 1 (IGF1R), a key signalling molecule in RMS.

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