Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TREX1 is required for microglial cholesterol homeostasis and subsequent oligodendrocyte maturation during brain development

ABSTRACT: TREX1 is required for microglial cholesterol homeostasis and subsequent oligodendrocyte maturation during brain development

PROVIDER: PRJNA895041 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR22065114_1.fastq.gz	Fastqsanger.gz
	SRR22065114_2.fastq.gz	Fastqsanger.gz
	SRR22065115_1.fastq.gz	Fastqsanger.gz
	SRR22065115_2.fastq.gz	Fastqsanger.gz
	SRR22065116_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 21

Similar Datasets

TREX1 is required for microglial cholesterol homeostasis and subsequent oligodendrocyte maturation during brain development [scRNA-seq]

Project description:Three Prime Repair Exonuclease 1 (TREX1) gene mutations have been associated with Aicardi-Goutières Syndrome (AGS) - a rare, severe pediatric autoimmune disorder that primarily affects the brain and has a poorly understood etiology. Microglia are brain-resident macrophages indispensable for brain development and implicated in multiple neuroinflammatory diseases. However, the role of TREX1 - a DNase that cleaves cytosolic nucleic acids, preventing viral- and autoimmune-related inflammatory responses - in microglia biology remains to be elucidated. Here, we leverage a model of human embryonic stem cell (hESC)-derived engineered microglia-like cells, bulk, and single-cell transcriptomics, optical and transmission electron microscopy, and three-month-old assembloids composed of microglia and oligodendrocyte-containing organoids to interrogate TREX1 functions in human microglia. Our analyses suggest that TREX1 influences cholesterol metabolism, leading to an active microglial morphology with increased phagocytosis in the absence of TREX1. Notably, regulating cholesterol metabolism with an HMG-CoA reductase inhibitor, FDA-approved atorvastatin, rescues these microglial phenotypes. Functionally, TREX1 in microglia is necessary for the transition from gliogenic intermediate progenitors known as pre-oligodendrocyte precursor cells (pre-OPCs) to precursors of the oligodendrocyte lineage known as OPCs, impairing oligodendrogenesis in favor of astrogliogenesis in human assembloids. Together, these results suggest routes for therapeutic intervention in pathologies such as AGS based on microglia-specific molecular and cellular mechanisms.

2024-10-08 | GSE216673 | GEO

TREX1 is required for microglial cholesterol homeostasis and subsequent oligodendrocyte maturation during brain development [bulk RNA-seq]

Project description:Three Prime Repair Exonuclease 1 (TREX1) gene mutations have been associated with Aicardi-Goutières Syndrome (AGS) – a rare, severe pediatric autoimmune disorder that primarily affects the brain and has a poorly understood etiology. Microglia are brain-resident macrophages indispensable for brain development and implicated in multiple neuroinflammatory diseases. However, the role of TREX1 – a DNase that cleaves cytosolic nucleic acids, preventing viral- and autoimmune-related inflammatory responses – in microglia biology remains to be elucidated. Here, we leverage a model of human embryonic stem cell (hESC)-derived engineered microglia-like cells, bulk and single-cell transcriptomics, optical and transmission electron microscopy, and three-month-old assembloids composed of microglia and regionalized neural organoids to interrogate TREX1 functions in human microglia. Our analyses suggest that TREX1 influences cholesterol metabolism, leading to an active microglial morphology with increased phagocytosis in the absence of TREX1. Notably, regulating cholesterol metabolism with an HMG-CoA reductase inhibitor, FDA-approved atorvastatin, rescues these microglial phenotypes. Functionally, TREX1-deficient microglia selectively affect oligodendrocyte maturation and myelination in assembloids. Together, these results suggest routes for therapeutic intervention in pathologies such as AGS based on microglia-specific molecular and cellular mechanisms.

2023-11-23 | GSE216702 | GEO

TREX1 is required for microglial cholesterol homeostasis and subsequent oligodendrocyte maturation during brain development [scRNA-seq]

Project description:TREX1 is required for microglial cholesterol homeostasis and subsequent oligodendrocyte maturation during brain development [scRNA-seq]

| PRJNA894940 | ENA

TREX1 is required for microglial cholesterol homeostasis and subsequent oligodendrocyte maturation during brain development [bulk RNA-seq]

Project description:TREX1 is required for microglial cholesterol homeostasis and subsequent oligodendrocyte maturation during brain development [bulk RNA-seq]

| PRJNA895014 | ENA

TREX1 is required for microglial cholesterol homeostasis and subsequent oligodendrocyte maturation during brain development

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

2023-11-23 | GSE216718 | GEO

The cholesterol transporter NPC1 is essential for epigenetic regulation and maturation of oligodendrocyte lineage cells snRNA-Seq

Project description:Cholesterol is required for oligodendrocyte maturation and CNS myelination. Here, we demonstrate an essential role for the intracellular cholesterol transporter NPC1 in these processes. NPC1 functions in late endosomes and lysosomes to efflux unesterified cholesterol, and its deficiency causes Niemann-Pick disease Type C, an autosomal recessive lysosomal disorder characterized by progressive neurodegeneration and early death. To identify cell types and pathways affected early in pathogenesis, we performed single nuclear RNA-seq on the forebrain of Npc1-/- mice at P16. This analysis uncovered striking transcriptional changes in the oligodendrocyte lineage during the period of developmental myelination, accompanied by diminished maturation of myelinating oligodendrocytes. Unexpectedly, we identified a significant upregulation of genes associated with neurogenesis and synapse formation in Npc1-/- oligodendrocyte lineage cells, reflecting diminished gene silencing by H3K27me3 and H3K9me3.

2023-05-31 | GSE221609 | GEO

Quetiapine induces oligodendrocyte precursor cell differentiation by cholesterol biosynthesis

Project description:Quetiapine induces oligodendrocyte precursor cell differentiation by cholesterol biosynthesis

| PRJNA515864 | ENA

The cholesterol transporter NPC1 is essential for epigenetic regulation and maturation of oligodendrocyte lineage cells ChIP-seq

2023-05-31 | GSE219007 | GEO

TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge

Project description:TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge

| PRJNA540829 | ENA

The cholesterol transporter NPC1 is essential for epigenetic regulation and maturation of oligodendrocyte lineage cells bulk RNA-seq of mouse OPCs

2023-05-31 | GSE221336 | GEO