Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GABAergic neuronal IL-4R mediates T cell effect on memory [WT + SCID]

ABSTRACT: The immune and nervous systems are highly interactive, however, little is known about how immune cells and their derived molecules impact brain function. Here we show that T cells play a critical role in retrieval of contextual fear conditioning (CFC) memory. Single-nuclei sequencing (snRNAseq) of engram neurons and non-engram neurons from the dentate gyrus one day after CFC learning revealed new evidence about differential expression of immune-related and synaptic plasticity-related genes, in SCID vs. wild-type mice. These findings present a comprehensive picture on how T cells and their derived cytokines could regulate memory retrieval and provide new insights into the nature of neuroimmune interactions at the transcriptional level in neurons. Overall, restoration of T cells or IL-4R signaling might lead to selective rescue of memory retrieval, and proffer a valuable strategy for treating memory loss.

ORGANISM(S): Mus musculus

PROVIDER: GSE143177 | GEO | 2021/10/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

GABAergic neuronal IL-4R mediates T cell effect on memory [Il4rkoT]

Project description:The immune and nervous systems are highly interactive, however, little is known about how immune cells and their derived molecules impact brain function. Here we show that T cells play a critical role in retrieval of contextual fear conditioning (CFC) memory. Single-nuclei sequencing (snRNAseq) of engram neurons and non-engram neurons from the dentate gyrus one day after CFC learning revealed new evidence about differential expression of immune-related and synaptic plasticity-related genes, in SCID vs. wild-type mice. These findings present a comprehensive picture on how T cells and their derived cytokines could regulate memory retrieval and provide new insights into the nature of neuroimmune interactions at the transcriptional level in neurons. Overall, restoration of T cells or IL-4R signaling might lead to selective rescue of memory retrieval, and proffer a valuable strategy for treating memory loss.

2021-10-12 | GSE143182 | GEO

GABAergic neuronal IL-4R mediates T cell effect on memory [Il4raFlox]

2021-10-12 | GSE143180 | GEO

Hippocampal neurons’ cytosolic and membrane-bound ribosomal transcript profiles are differentially regulated by learning and subsequent sleep

Project description:The hippocampus is essential for consolidating transient experiences into long-lasting memories. Memory consolidation is facilitated by postlearning sleep, although the underlying cellular mechanisms are largely unknown. We took an unbiased approach to this question by using a mouse model of hippocampally mediated, sleep-dependent memory consolidation (contextual fear memory). Because synaptic plasticity is associated with changes to both neuronal cell membranes (e.g., receptors) and cytosol (e.g., cytoskeletal elements), we characterized how these cell compartments are affected by learning and subsequent sleep or sleep deprivation (SD). Translating ribosome affinity purification was used to profile ribosome-associated RNAs in different subcellular compartments (cytosol and membrane) and in different cell populations (whole hippocampus, Camk2a+ neurons, or highly active neurons with phosphorylated ribosomal subunit S6 [pS6+]). We examined how transcript profiles change as a function of sleep versus SD and prior learning (contextual fear conditioning; CFC). While sleep loss altered many cytosolic ribosomal transcripts, CFC altered almost none, and CFC-driven changes were occluded by subsequent SD. In striking contrast, SD altered few transcripts on membrane-bound (MB) ribosomes, while learning altered many more (including long non-coding RNAs [lncRNAs]). The cellular pathways most affected by CFC were involved in structural remodeling. Comparisons of post-CFC MB transcript profiles between sleeping and SD mice implicated changes in cellular metabolism in Camk2a+ neurons and protein synthesis in highly active pS6+ (putative "engram") neurons as biological processes disrupted by SD. These findings provide insights into how learning affects hippocampal neurons and suggest that the effects of SD on memory consolidation are cell type and subcellular compartment specific.

2022-10-25 | GSE216163 | GEO

Recapitulation of endogenous 4R tau expression and formation of insoluble tau in directly reprogrammed human neurons

Project description:Tau is a microtubule-binding protein expressed in neurons and the equal ratio between 4-repeat (4R) and 3-repeat (3R) isoforms are maintained in normal adult brain function. Dysregulation of 3R:4R ratio causes tauopathy and human neurons that recapitulate tau isoforms in health and disease will provide a platform for elucidating pathogenic processes involving tau pathology. We carried out extensive characterizations of tau isoforms expressed in human neurons derived by microRNA-induced neuronal reprogramming of adult fibroblasts. Transcript and protein analyses showed miR-neurons expressed all six isoforms with the 3R:4R isoform ratio equivalent to that detected in human adult brains. Also, miR-neurons derived from familial tauopathypatients with a 3R:4R ratio altering mutation showed increased 4R tau and the formation of insoluble tau with seeding activity. Our results collectively demonstrate the utility of miRNA-induced neuronal reprogramming to recapitulate endogenous tau regulation comparable to the adult brain in health and disease.

2022-04-26 | GSE201084 | GEO

Human iPSC 4R tauopathy model uncovers modifiers of tau propagation [scRNA-seq]

Project description:Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to lack of appropriate human models. Here, we engineered new human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity. A CRISPRi screen of genes associated with Tau pathobiology identified over 500 genetic modifiers of seeding-induced Tau propagation, including retromer VPS29 and genes in the UFMylation cascade. In progressive supranuclear palsy (PSP) and Alzheimer’s Disease (AD) brains, the UFMylation cascade is altered in neurofibrillary-tangle-bearing neurons. Inhibiting the UFMylation cascade in vitro and in vivo suppressed seeding-induced Tau propagation. This model provides a robust platform to identify novel therapeutic strategies for 4R tauopathy.

2024-04-08 | GSE255904 | GEO

Human iPSC 4R tauopathy model uncovers modifiers of tau propagation [bulk RNA-seq]

2024-04-08 | GSE255902 | GEO

GABAergic neuronal IL-4R mediates T cell effect on memory [WT + SCID]

Project description:GABAergic neuronal IL-4R mediates T cell effect on memory [WT + SCID]

| PRJNA599139 | ENA

Engram-specific transcriptome profiling of contextual memory consolidation

Project description:Sparse populations of neurons in the dentate gyrus (DG) of the hippocampus are causally implicated in the encoding of contextual fear memories. However, engram-specific molecular mechanisms underlying memory consolidation remain largely unknown. Here we perform unbiased RNA sequencing of DG engram neurons 24h after contextual fear conditioning to identify transcriptome changes specific to memory consolidation. DG engram neurons exhibit a highly distinct pattern of gene expression, in which CREB-dependent transcription features prominently (P=6.2x10-13), including Atf3 (P=2.4x10-41), Penk (P=1.3x10-15), and Kcnq3 (P=3.1x10-12). Moreover, we validate the functional relevance of the RNAseq findings by establishing the causal requirement of intact CREB function specifically within the DG engram during memory consolidation, and identify a novel group of CREB target genes involved in the encoding of long-term memory.

2019-03-30 | GSE129024 | GEO

Microbacterium sp. 4R-513

Project description:Microbacterium sp. 4R-513 Genome sequencing

| PRJNA607820 | ENA

GABAergic neuronal IL-4R mediates T cell effect on memory

Project description:GABAergic neuronal IL-4R mediates T cell effect on memory

| PRJNA599150 | ENA