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Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance [ATAC-seq]

ABSTRACT: Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance [ATAC-seq]

PROVIDER: PRJNA848774 | ENA |

REPOSITORIES: ENA

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Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance

Project description:Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance

| PRJNA848763 | ENA

Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance [RNA-seq]

Project description:Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance [RNA-seq]

| PRJNA848772 | ENA

Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance [ATAC-seq]

Project description:Many human cancers, including acute myeloid leukemia (AML), arise from mutations of stem and progenitor cells. Immunophenotypic profiling has shown that leukemia develops hierarchically, with mutations in leukemia stem cells associated with disease propagation and relapse1,2. Although leukemia initiating cells can be enriched using cell surface markers, their frequency tends to be variable and low, obscuring mechanisms and hindering effective therapies3,4. To define AML stem cells in human patients, we performed functional genomic profiling of diverse leukemias using label tracing techniques designed to preserve hematopoietic stem cell (HSC) function in vivo. We found that propagation of human AML is mediated by a rare but distinct quiescent label-retaining cell (LRC) population that evades detection by currently known immunophenotypic markers. We show that human AML LRC quiescence is reversible, sparing genetic clonal competition that maintains its epigenetic inheritance. LRC quiescence is defined by distinct promoter-centered chromatin and gene expression dynamics, and controlled by a novel AP-1/ETS transcription factor network, which is associated with disease persistence and chemotherapy resistance in diverse patients. These results enable prospective isolation and functional genetic manipulation of immunophenotypically-varied leukemia stem cells in human patient specimens, as well as establish the key functions of epigenetic plasticity in leukemia development and therapy resistance. We anticipate that these findings will lead to the elucidation of essential properties of leukemia stem cell quiescence and the design of therapeutic strategies for their clinical identification and control.

2024-06-28 | GSE205989 | GEO

Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance [RNA-seq]

2024-06-28 | GSE205993 | GEO

Mechanisms Controlling Human Microglia Gene Expression

Project description:Mechanisms Controlling Human Microglia Gene Expression

| PRJNA388723 | ENA

Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-06-28 | GSE205994 | GEO

Project description:SAGA and ATAC are two related transcriptional coactivator complexes, sharing the same histone acetyltransferase (HAT) subunit. The HAT activities of SAGA and ATAC are required for metazoan development but the precise role of the two complexes in RNA polymerase II transcription in mammals is less understood. To determine whether SAGA and ATAC have redundant or specific functions dependent on their HAT activities, we compared the effects of HAT inactivation in each complex with that of inactivation of either SAGA or ATAC core subunits in mouse embryonic stem cells (ESCs). We show that core subunits of SAGA or ATAC subunits are required for complex assembly, mouse ESC growth and self-renewal. Additionally, ATAC, but not SAGA subunits are required for ESC viability by regulating the transcription of translation-related genes. Surprisingly, depletion of specific or shared HAT module subunits caused a global decrease in histone H3K9 acetylation, but did not result in significant phenotypic or transcriptional defects. Thus, our results indicate that SAGA and ATAC are differentially required for viability and self-renewal of mouse ESCs by regulating transcription through different pathways, in a HAT-independent manner.

2021-08-11 | PXD027026 | Pride

Mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance

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Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis

Project description:Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis

| PRJNA987620 | ENA