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Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in Desmoplastic Small Round Cell Tumors

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE263523 | GEO | 2024/04/15

REPOSITORIES: GEO

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Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in Desmoplastic Small Round Cell Tumors [snMultiome]

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Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in Desmoplastic Small Round Cell Tumors

Project description:Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in Desmoplastic Small Round Cell Tumors

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Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in Desmoplastic Small Round Cell Tumors [snMultiome]

Project description:Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in Desmoplastic Small Round Cell Tumors [snMultiome]

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Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in DSRCTs.

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 12 samples from five patients, we find that DSRCT tumor cells cluster into consistent subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs. In vitro modeling shows that high EWSR1::WT1 DNA-binding activity associates with most lineage-related states, in contrast to glycolytic and profibrotic states. Single-cell chromatin accessibility analysis suggests that EWSR1::WT1 binding site variability may drive distinct lineage-related transcriptional programs, supporting some level of cell-intrinsic plasticity. Spatial transcriptomics reveals that glycolytic and profibrotic states specifically localize within hypoxic niches at the periphery of tumor cell islets, suggesting an additional role of tumor cell-extrinsic microenvironmental cues. We finally identify a single-cell transcriptomics-derived epithelial signature associated with improved patient survival, highlighting the clinical relevance of our findings.

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