Project description:Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1-WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on samples from patients, we find that DSRCT tumor cells cluster into consistant subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs.
Project description:Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1-WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on samples from patients, we find that DSRCT tumor cells cluster into consistant subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs.
Project description:Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1-WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on samples from patients, we find that DSRCT tumor cells cluster into consistant subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs.
Project description:Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1-WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on samples from patients, we find that DSRCT tumor cells cluster into consistant subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs.
Project description:Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1-WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on samples from patients, we find that DSRCT tumor cells cluster into consistant subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs.
Project description:Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1-WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on samples from patients, we find that DSRCT tumor cells cluster into consistant subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs.
Project description:Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1-WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on samples from patients, we find that DSRCT tumor cells cluster into consistant subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs.
Project description:To determine whether sarcomas – tumors of mesenchymal origin – are subject to the same technical artifacts, we profiled patient-derived tumor explants (PDXs) propagated from three aggressive subtypes: osteosarcoma, Ewing sarcoma (ES), desmoplastic small round cell tumor (DSRCT). Given the rarity of these sarcoma subtypes, we explored whether single-nuclei RNA-seq from more widely available archival frozen specimens could accurately be identified by gene expression signatures linked to tissue phenotype or pathognomonic fusion proteins.
Project description:Regulatory T cells (Tregs) can impair anti-tumor immune responses and are associated with poor prognosis in multiple cancer types. Tregs in human tumors span diverse transcriptional states distinct from those of peripheral Tregs, but their contribution to tumor development remains unknown. Here, we use single cell RNA-Seq to longitudinally profile dynamic shifts in the distribution of Tregs in a genetically-engineered mouse model of lung adenocarcinoma. In this model, interferon-responsive Tregs are more prevalent early in tumor development, while a specialized effector phenotype characterized by enhanced expression of the interleukin 33 receptor ST2 is predominant in advanced disease. Treg-specific deletion of ST2 alters the evolution of effector Treg diversity, increases infiltration of CD8+ T cells into tumors, and decreases tumor burden. Our study shows that ST2 plays a critical role in Treg-mediated immunosuppression in cancer, highlighting potential paths for therapeutic intervention.