RNA-seq of Arc/Arg3.1-positive versus Arc/Arg3.1-negative skin migratory dendritic cells from healthy mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA477512 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7412103.fastq.gz | Fastqsanger.gz | |||
| SRR7412104.fastq.gz | Fastqsanger.gz | |||
| SRR7412105.fastq.gz | Fastqsanger.gz | |||
| SRR7412106.fastq.gz | Fastqsanger.gz |
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Project description:The key function of migratory dendritic cells (migDCs) is to take up antigens in peripheral tissues and migrate to draining lymph nodes (dLN) to initiate immune responses. Recently, we discovered in mice that in the immune system activity-regulated cytoskeleton associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) is exclusively expressed by migDCs and is a central driver of fast inflammatory migration. However, the frequency of Arc/Arg3.1 expressing cells in different migDC subsets including Langerhans cells (LC), their phylogenetic origin, transcription factor dependency and functional role remains unclear. Here we found that Arc/Arg3.1+ migDCs derived from common DC precursors (CDPs) and radio-resistant LCs. They were present in all migDC subsets and showed a consistent superiority in inflammatory migration but were independent of the transcription factors Irf4 or Batf3. In intradermal Staphylococcus aureus infection, a model that relies on effective inflammatory antigen transport, Arc/Arg3.1 deletion strongly reduced T cell responses. By contrast, Arc/Arg3.1 deficiency did not hamper the immune response to systemic Listeria monocytogenes infection, which does not require antigen transport. Thus, our results show that Arc/Arg3.1 is a molecular marker for defining a population of DCs with superior migratory capacity that spans across all migDC subsets irrespective of ontogeny and phenotype.
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Project description:We compared the expression profiles of bone marrow-derived dendritic cells (BMDC) derived from Arc/Arg3.1 knockout and wildtype animals. We generated bone marrow-derived dendritic cells (BMDC) from Arc/Arg3.1 knockout and wildtype animals. BMDC were either stimulated with LPS or left untreated and analysed by microarray.
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Project description:We compared the expression profiles of bone marrow-derived dendritic cells (BMDC) derived from Arc/Arg3.1 knockout and wildtype animals.
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Project description:Arc is an activity regulated neuronal protein yet little is known about its protein interactions, assembly into multiprotein complexes, role in human disease and cognition. We applied an integrated proteomic and genetic strategy using targeted tagging of a Tandem Affinity Purification (TAP) tag and Venus fluorescent protein into the endogenous Arc gene in mice, biochemical and proteomic characterization of native complexes in wild type and knockout mice, and human genetic analyses of disease and intelligence. TAP tagging enabled efficient purification of complexes and identification of many novel Arcinteracting proteins, of which PSD95 was the most abundant. PSD95 was essential for Arc assembly into 1.5 MDa complexes and activity-dependent recruitment to excitatory synapses. Integrating human genetic data with proteomic data showed postsynaptic Arc- PSD95 complexes are enriched in schizophrenia, intellectual disability, autism and epilepsy mutations and normal variants in intelligence. Arc-PSD95 postsynaptic complexes are a molecular substrate for the convergence of normal and pathological genetic variants impacting on human cognitive function.
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