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Microglia in developing retina transition through a disease-like functional state that does not require CSF1R signaling for survival

ABSTRACT: Microglia in developing retina transition through a disease-like functional state that does not require CSF1R signaling for survival

PROVIDER: PRJNA509754 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8315010.fastq.gz	Fastqsanger.gz
	SRR8315011.fastq.gz	Fastqsanger.gz
	SRR8315012.fastq.gz	Fastqsanger.gz
	SRR8315013.fastq.gz	Fastqsanger.gz
	SRR8315004.fastq.gz	Fastqsanger.gz

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Microglia in developing retina transition through a disease-like functional state that does not require CSF1R signaling for survival

Project description:Microglia have important remodeling functions in development and disease. There is evidence for molecular diversity of microglia suggesting they may exist in distinct functional states to differentially impact CNS health and function. To better understand this in development, we profiled microglia of a discrete developing CNS region, the murine retina. We find that retinal microglia transition through unique transcriptional states and identify a population with peak density postnatally that resemble adult disease-associated microglia (DAM) and CD11c+ microglia of developing white matter, we term DAM-like. Developmental cell death is a major driver of the DAM-like phenotype, and TREM2 signaling is required for select DAM gene expression. Notably, DAM-like cells that highly express CD11c are not dependent on CSF1R signaling for survival, and TREM2 signaling is required for CSF1R independence in a subset of microglia. Thus, microglial phenotype in development is influenced by local developmental events and may share features with microglia in disease.

2019-06-10 | GSE123757 | GEO

CSF1R-CAR T cells induce CSF1R signaling and promote target cell growth

Project description:Chimeric antigen receptor (CAR) T cells have revolutionized the landscape of cancer therapy, demonstrating unprecedented success in treating relapsed or refractory blood cancers. Previous studies of the mechanisms underlying the interactions and responses of CAR T cells and their targets have focused on the activation of CAR T cells and attempted to optimize CAR design to increase efficacy, while ignoring tumors and their responses to CAR ligation. We evaluated the signaling of a second-generation, ligand-based CAR built from the colony-stimulating factor 1 (CSF1) ligand to target the CSF1 receptor (CSF1R) on CSF1R-expressing target cells, and compared it to a conventional single-chain variable fragment (scFv)–based CAR against the B-cell antigen CD19 using stable isotope labeling by amino acids in cell culture (SILAC) co-culture with phosphotyrosine (pY) enrichment and liquid chromatography–tandem mass spectrometry (LC–MS/MS).. We showed that ligation of CSF1R-expressing THP-1 cells with CSF1R-CAR T cells stimulated CSF1R-like signaling in the THP-1 cells, whereas no target cell signaling response was observed after the ligation of CD19-CAR T cells with target Raji cells. In experiments with small-molecule inhibitors of the tyrosine kinase Lck, actin polymerization, and CSF1R, we found that CAR-induced CSF1R signaling in THP-1 cells depended exclusively on the kinase activity of CSF1R with no participation from T cell activation. Consistently, CSF1R-CAR T cells promoted THP-1 cell growth at low effector-to-target (E:T) ratios but prevented THP-1 cell growth at high E:T ratios. Our data provide evidence for an unintended consequence of CARs: CAR-induced signaling in cancer cells. These data may have broad implications for the choice of CAR antigen for optimal clinical efficacy.

2025-11-21 | PXD058576 | Pride

Molecular anatomy of the developing human retina

Project description:Molecular anatomy of the developing human retina

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scRNA-seq of the developing human retina

Project description:scRNA-seq of the developing human retina

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scRNA-seq of the developing human retina

Project description:Time-series of single-cell RNA-sequencing performed on stem cell derived retinal organoids or post-mortem tissue from the developing and adult retina

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R7-dependent transcription in the developing Drosophila retina

Project description:R7-dependent transcription in the developing Drosophila retina

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RNA-seq analysis of the developing chicken retina

Project description:The chicken embryo (Gallus gallus) is a classic model system for studying developmental biology. During chick development, embryonic day 8 (E8) retina are packed with multipotent neuronal precursors on the cusp of differentiation into all retinal cell types. By E18 the retina is nearly fully mature with all major retinal cell types differentiated and expressing cell type-specific genes. Whole retina were harvested from embryonic day 8 (E8), E16, and E18 developing chicken embryos. Whole cornea were also collected from E18 embryos as a reference tissue. Duplicates were obtained for each time point and total RNA was extracted from samples using a Qiagen AllPrep Mini Kit. To characterize differential gene expression in these tissues, Illumina stranded TrueSeq RNA-Seq libraries were prepared from total RNA and 125 PE sequencing reads were obtained. These data will be used to characterize retina-specific patters of gene expression as well as global changes in gene expression between critical developmental time points in the chicken retina.

2016-08-18 | GSE65938 | GEO

Differential expression of genes in photoreceptor and other retinal cells in developing retina

Project description:To analyze cell lineage specific global transcriptional changes during retinogenesis, we sequenced mRNA from developing retina fractioned to Cd73+ photoreceptors and Cd73- other cells, in addition to the whole retina at embryonic period.

2016-07-28 | GSE71462 | GEO

Molecular anatomy of the developing human retina

Project description:Clinical and genetic heterogeneity associated with retinal diseases makes stem cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 150. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared to peripheral retina. Human and mouse retinal transcriptomes show remarkable similarity in developmental stages, though morphogenesis was greatly expanded in humans. Integration of DNA accessibility data allowed us to reconstruct transcriptional networks controlling photoreceptor differentiation. Our studies provide insights into human retinal development and serve as resource for molecular staging of human stem cell-derived retinal organoids.

2017-12-07 | GSE104827 | GEO

Ronin transcriptional target genes in the developing mouse retina

Project description:Ronin transcriptional target genes in the developing mouse retina

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