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CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10

ABSTRACT: CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10

PROVIDER: PRJNA552982 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9648710_1.fastq.gz	Fastqsanger.gz
	SRR9648710_2.fastq.gz	Fastqsanger.gz
	SRR9648711_1.fastq.gz	Fastqsanger.gz
	SRR9648711_2.fastq.gz	Fastqsanger.gz
	SRR9648706_1.fastq.gz	Fastqsanger.gz

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CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10

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CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10

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CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10 [R07_Cx3cr1]

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CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10 [R10_PD-L1+VISTA treatment]

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CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10.

Project description:Brain metastasis (br-met) develops in an immunologically unique br-met niche. Central nervous system-native myeloid cells (CNS-myeloids) and bone-marrow-derived myeloid cells (BMDMs) cooperatively regulate brain immunity. The phenotypic heterogeneity and specific roles of these myeloid subsets in shaping the br-met niche to regulate br-met outgrowth have not been fully revealed. Applying multimodal single-cell analyses, we elucidated a heterogeneous but spatially defined CNS-myeloid response during br-met outgrowth. We found Ccr2+ BMDMs minimally influenced br-met while CNS-myeloid promoted br-met outgrowth. Additionally, br-met-associated CNS-myeloid exhibited downregulation of Cx3cr1. Cx3cr1 knockout in CNS-myeloid increased br-met incidence, leading to an enriched interferon response signature and Cxcl10 upregulation. Significantly, neutralization of Cxcl10 reduced br-met, while rCxcl10 increased br-met and recruited VISTAHi PD-L1+ CNS-myeloid to br-met lesions. Inhibiting VISTA- and PD-L1-signaling relieved immune suppression and reduced br-met burden. Our results demonstrate that loss of Cx3cr1 in CNS-myeloid triggers a Cxcl10-mediated vicious cycle, cultivating a br-met-promoting, immune-suppressive niche.

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CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10

Project description:We used CITE-seq (10x Gemoics-based) to profile and compare the transcriptomes and cell surface expression of a set of immune markers of naïve brain myeloid cells from wild type C57Bl/6 mice to brain metastasis-associated myeloid cells (Br.MAM) from C57Bl/6 mice bearing E0771 brain metastases. In each sequencing round, we sequenced a total of four different mouse brains (2 naive and 2 metastasis-burdened). We created an antibody pool consisting of 6 different antibodies (CD45, CD25, CD3, CD4, CD11b, and CD86) and stained each brain individually with this antibody pool. Then, we stained each brain with it's own unique hashing antibody so that we could subsequently pool the samples for loading onto the 10x Chromium and later prepare one library consisting of all six samples and finally separate each sample in silico by it's unique hashing antibody.

2020-10-29 | GSE134284 | GEO

CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10

Project description:We used CITE-seq (10x Genomics-based) to profile and compare the transcriptomes and cell surface expression of a set of immune markers of naïve brain myeloid cells from wild type C57BL/6 mice to brain metastasis-associated myeloid cells (Br.MAM) from C57BL/6 mice bearing E0771 brain metastases. In each sequencing round, we sequenced a total of four different mouse brains (2 naive and 2 metastasis-burdened). We created an antibody pool consisting of 6 different antibodies (CD45, CD25, CD3, CD4, CD11b, and CD86) and stained each brain individually with this antibody pool. Then, we stained each brain with it's own unique hashing antibody so that we could subsequently pool the samples for loading onto the 10x Chromium and later prepare one library consisting of all six samples and finally separate each sample in silico by it's unique hashing antibody.

2020-10-29 | GSE133905 | GEO

CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10

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

2020-10-29 | GSE134285 | GEO