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Cell State Dependent Alteration of Melanoma Plasticity and Immunity by the Circadian Transcription Factor Bmal1

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

ORGANISM(S): Mus musculus

PROVIDER: GSE202289 | GEO | 2023/05/04

REPOSITORIES: GEO

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Cell State Dependent Alteration of Melanoma Plasticity and Immunity by the Circadian Transcription Factor Bmal1 [ChIP-Seq]

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Project description:Cell State Dependent Alteration of Melanoma Plasticity and Immunity by the Circadian Transcription Factor Bmal1

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Cell State Dependent Alteration of Melanoma Plasticity and Immunity by the Circadian Transcription Factor Bmal1 [RNA-Seq]

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Cell State Dependent Alteration of Melanoma Plasticity and Immunity by the Circadian Transcription Factor Bmal1 [scRNA-Seq]

Project description:Cell State Dependent Alteration of Melanoma Plasticity and Immunity by the Circadian Transcription Factor Bmal1 [scRNA-Seq]

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Cell State Dependent Alteration of Melanoma Plasticity and Immunity by the Circadian Transcription Factor Bmal1 [ChIP-Seq II]

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Cell state dependent effects of Bmal1 on melanoma immunity and tumorigenicity.

Project description:The circadian clock regulator Bmal1 modulates tumorigenesis, but its reported effects are inconsistent. Here, we show that Bmal1 has a context-dependent role in mouse melanoma tumor growth. Loss of Bmal1 in YUMM2.1 or B16-F10 melanoma cells eliminates clock function and diminishes hypoxic gene expression and tumorigenesis, which could be rescued by ectopic expression of HIF1α in YUMM2.1 cells. By contrast, over-expressed wild-type or a transcriptionally inactive mutant Bmal1 non-canonically sequester myosin heavy chain 9 (Myh9) to increase MRTF-SRF activity and AP-1 transcriptional signature, and shift YUMM2.1 cells from a Sox10high to a Sox9high immune resistant, mesenchymal cell state that is found in human melanomas. Our work describes a link between Bmal1, Myh9, mouse melanoma cell plasticity, and tumor immunity. This connection may underlie cancer therapeutic resistance and underpin the link between the circadian clock, MRTF-SRF and the cytoskeleton.

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