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Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer

ABSTRACT: Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer

PROVIDER: PRJNA779401 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16904616_1.fastq.gz	Fastqsanger.gz
	SRR16904616_2.fastq.gz	Fastqsanger.gz
	SRR16904617_1.fastq.gz	Fastqsanger.gz
	SRR16904617_2.fastq.gz	Fastqsanger.gz
	SRR16904618_1.fastq.gz	Fastqsanger.gz

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Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer

Project description:The tumor immune microenvironment (TIME) is commonly infiltrated by diverse collections of myeloid cells. Yet, the complexity of myeloid cell identity and plasticity has challenged efforts to define bona fidepopulations and determine their connections to T cell functionand their relation to patient outcome. Here we leverage single-cell RNA-sequencing (scRNA-seq) analysis of several mouse and human tumors and find that monocyte-macrophage diversity is characterized by a combination of conserved lineage states as well as transcriptional programs accessed along the differentiation trajectory. Using mouse models, we also find that tumor monocyte-to-macrophage progression is profoundly tied to regulatory T cell (Treg) abundance. Importantly, in human kidney cancer, heterogeneity in macrophage accumulation and myeloid composition corresponded to variancein, not only Tregdensity, but also the quality of infiltrating CD8+T cells.In this way, holistic analysis of monocyte-to-macrophage differentiation creates a framework for critically different immune states

2022-04-27 | GSE188548 | GEO

Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer.

Project description:The tumor immune microenvironment (TIME) is commonly infiltrated by diverse collections of myeloid cells. Yet, the complexity of myeloid-cell identity and plasticity has challenged efforts to define bona fide populations and determine their connections to T-cell function and their relationship to patient outcome. Here, we have leveraged single-cell RNA-sequencing analysis of several mouse and human tumors and found that monocyte-macrophage diversity is characterized by a combination of conserved lineage states as well as transcriptional programs accessed along the differentiation trajectory. We also found in mouse models that tumor monocyte-to-macrophage progression was profoundly tied to regulatory T cell (Treg) abundance. In human kidney cancer, heterogeneity in macrophage accumulation and myeloid composition corresponded to variance in, not only Treg density, but also the quality of infiltrating CD8+ T cells. In this way, holistic analysis of monocyte-to-macrophage differentiation creates a framework for critically different immune states.

| S-EPMC8982148 | biostudies-literature

A p53-CCF circuit integrates genome integrity with senescence phenotypes

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Project description:Synthetic biology has focused on engineering genetic modules that operate orthogonally from the host cells. A synthetic circuit, however, can be designed to reprogram the host proteome, which in turn enhances the function of the synthetic circuit. Here, we apply this holistic synthetic biology concept by exploiting the crosstalk between metabolic networks in cells, leading to a protein environment more favorable for protein synthesis. Specifically, we show that a local module expressing translation machinery can reprogram the bacterial proteome, changing the expression levels of more than 780 proteins. The integration of the proteins synthesized by the local modules and the reprogramed proteome generate a cell-free system that can synthesize a diverse set of proteins in different reaction formats, with up to 5-fold higher expression level than classical cell-free systems. Our work demonstrates a holistic approach that integrates synthetic and systems biology concepts. This approach has the potential to achieve outcomes not possible by only local, orthogonal circuits.

2020-05-14 | PXD018858 | Pride

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