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Chromatin accessibility profiling of freshly isolated mouse lung cancer LLC- and breast cancer 4T1- derived leptomeningeal metastatic cancer cells from different anatomical locations [ATAC-Seq]

ABSTRACT: Chromatin accessibility profiling of freshly isolated mouse lung cancer LLC- and breast cancer 4T1- derived leptomeningeal metastatic cancer cells from different anatomical locations [ATAC-Seq]

PROVIDER: PRJNA1168110 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30863900_1.fastq.gz	Fastqsanger.gz
	SRR30863900_2.fastq.gz	Fastqsanger.gz
	SRR30863901_1.fastq.gz	Fastqsanger.gz
	SRR30863901_2.fastq.gz	Fastqsanger.gz
	SRR30863902_1.fastq.gz	Fastqsanger.gz

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Profiling of freshly isolated mouse lung cancer LLC- and mouse breast cancer 4T1- derived leptomeningeal metastatic cancer cells from different anatomical locations

Project description:Profiling of freshly isolated mouse lung cancer LLC- and mouse breast cancer 4T1- derived leptomeningeal metastatic cancer cells from different anatomical locations

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Transcriptomic profiling of freshly isolated mouse lung cancer LLC- and mouse breast cancer 4T1- derived leptomeningeal metastatic cancer cells from different anatomical locations [RNA-Seq]

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Chromatin accessibility profiling of freshly isolated mouse lung cancer LLC- and breast cancer 4T1- derived leptomeningeal metastatic cancer cells from different anatomical locations [ATAC-Seq]

Project description:Cancer cells metastatic to the leptomeninges encounter a metabolically-challenging extreme microenvironment. To understand adaptations to this space, we subjected leptomeningeal-metastatic (LeptoM) mouse breast and lung cancers isolated from either the leptomeninges or orthotopic primary sites to ATAC- and RNA-sequencing. When inhabiting the leptomeninges, the LeptoM cells demonstrated transcription downstream of retinoid-X-receptors (RXRs). We found evidence of local retinoic acid (RA) generation in both human leptomeningeal metastasis and mouse models in the form of elevated spinal fluid retinol and expression of RA-generating dehydrogenases within the leptomeningeal microenvironment. Stimulating LeptoM cells with 9-cis RA induced expression of transcripts encoding de novo fatty acid synthesis pathway enzymes in vitro. In vivo, whereas knockout of Stra6 did not alter cancer cell leptomeningeal growth, knockout of Rxra/b/g interrupted cancer cell lipid biosynthesis and arrested cancer growth. These observations illustrate a mechanism whereby locally-generated developmental cues metabolically reprogram metastatic cancer cells and suggest novel therapeutic approaches.

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Transcriptomic profiling of freshly isolated mouse lung cancer LLC- and mouse breast cancer 4T1- derived leptomeningeal metastatic cancer cells from different anatomical locations [RNA-Seq]

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Single-cell atlas of dura cells from non-tumor or leptomeningeal metastasis mice

Project description:We performed scRNA-seq on the cells isolated from the dura mater in non-tumor control mice and leptomeningeal metastasis (LM) mice with LLC-LeptoM cell inoculation for 7 or 12 days.

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Profiling of freshly isolated mouse lung cancer LLC- and mouse breast cancer 4T1- derived leptomeningeal metastatic cancer cells from different anatomical locations

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

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Transcriptomic profiling of LLC LeptoM vector control, Nr1h2/3 DKO and RXRa/b/g TKO upon stimulation with 1μM 9 cis-retinoic acid (RA) in vitro

Project description:To understand transcriptional regulation of nuclear receptors, LXRs and RXRs, in leptomeningeal metastatic cancer cells, we use CRISPR-Cas9 to knockout Nr1h2/3 genes (encoding LXRβ/α) or RXRa/b/g genes (encoding RXRα/β/γ) in LLC LeptoM cell lines, with small guide RNA targeting lacZ as vector control. We then subjected these cell lines for bulk RNA sequencing with or without stimulation of 1μM 9 cis-RA. Pathway analysis of the differentially expressed genes between LLC LeptoM vector control with RA stimulation to DMSO treatment revealed upregulation of developmental related pathways and lipid metabolism pathways. Meanwhile, loss of function in LXR or RXR both resulted in dysregulation of multiple lipid metabolism pathways, in which RXR made a broader impact.

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Project description:Cerebrospinal fluid cells derived from one breast cancer leptomeningeal metastases patient

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