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Single cell analyses reveals a non-canonical EZH2 activity as main driver of RA resistance in PLZF/RARA leukemia [scATAC-seq]

ABSTRACT: Single cell analyses reveals a non-canonical EZH2 activity as main driver of RA resistance in PLZF/RARA leukemia [scATAC-seq]

PROVIDER: PRJNA751034 | ENA |

REPOSITORIES: ENA

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Single cell analyses reveals a non-canonical EZH2 activity as main driver of RA resistance in PLZF/RARA leukemia [RNA-seq]

Project description:Resistance to treatment is due to the heterogeneity of the tumor which contains a subset of cancer cells that escape treatment and are responsible for the relapse. We took advantage of the PLZF/RARA retinoic acid (RA) resistant acute promyelocytic leukemia (APL) model to catch relapse-initiating cell features and their vulnerabilities. By developing an integrative single-cell multi-omics analysis (scRNA-seq and scATAC-seq), we uncovered transcriptional and chromatin heterogeneity of the PLZF/RARA APL blasts. We highlighted a subset of cells insensitive to RA-induced differentiation with a strong DNA repair signature ("Rep" cluster) and exhibiting a fine tuned transcriptional network targeting the histone methyltransferase Ezh2. Combining epigenomic profiling with mouse-derived models for Ezh2 catalytic inhibition or total KO, we revealed an independent methyltransferase Ezh2 activity linked to RA resistance. These findings demonstrate the power of single-cell multi-omics integration to highlight paths to sensitize therapy-resistant leukemia cells

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Single cell analyses reveals a non-canonical EZH2 activity as main driver of RA resistance in PLZF/RARA leukemia.

Project description:Single cell analyses reveals a non-canonical EZH2 activity as main driver of RA resistance in PLZF/RARA leukemia.

| PRJNA751028 | ENA

Transcription profiling of human U937T:PLZF-RARa Inducible Cells

Project description:The PLZF-RARa fusion oncoprotein is overexpressed in the t(11;17) subtype of acute promyelocytic leukemia. Gene expression microarrays were used to identify genes involved in leukemic transformation. We used microarray to detect gene expression changes induced by the PLZF-RARa fusion oncoprotein in the U937 cell line Experiment Overall Design: The U937T:PLZF-RARa cell line was engineered to express PLZF-RARa upon tetracycline removal. PLZF-RARa was induced for 48hr and RNA was extracted and hybridized to Affymetrix HGU133Plus2.0 Chips

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Single cell analyses reveals a non-canonical EZH2 activity as main driver of RA resistance in PLZF/RARA leukemia [RNA-seq]

Project description:Single cell analyses reveals a non-canonical EZH2 activity as main driver of RA resistance in PLZF/RARA leukemia [RNA-seq]

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Single cell analyses reveals a non-canonical EZH2 activity as main driver of RA resistance in PLZF/RARA leukemia [ChIP-seq]

Project description:Single cell analyses reveals a non-canonical EZH2 activity as main driver of RA resistance in PLZF/RARA leukemia [ChIP-seq]

| PRJNA751031 | ENA

Single cell analyses reveals a non-canonical EZH2 activity as main driver of RA resistance in PLZF/RARA leukemia [scRNA-seq]

Project description:Single cell analyses reveals a non-canonical EZH2 activity as main driver of RA resistance in PLZF/RARA leukemia [scRNA-seq]

| PRJNA751033 | ENA