Olfactory receptor accessory proteins play crucial roles in receptor gene choice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE87694 | GEO | 2017/03/01
SECONDARY ACCESSION(S): PRJNA345584
REPOSITORIES: GEO
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Project description:Olfactory sensory neurons (OSNs) transform the stochastic choice of one out of >1000 olfactory receptor (OR) genes into precise and stereotyped axon targeting of OR-specific glomeruli in the olfactory bulb. Here, we show that the PERK arm of the unfolded protein response (UPR) regulates both the glomerular coalescence of like axons, and the specificity of their projections. Subtle differences in OR protein sequences lead to distinct patterns of endoplasmic reticulum (ER) stress during OSN development, converting OR identity into distinct gene expression signatures. We identify the transcription factor Ddit3 as a key effector of PERK signaling that maps OR-dependent ER signaling patterns to the transcriptional regulation of axon guidance and cell adhesion genes, instructing targeting precision. Our results extend the known functions of the UPR from a quality control pathway that protects cells from misfolded proteins, to a sensor of cellular identity that interprets physiological states to direct axon wiring.
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Project description:Olfaction plays important roles in food and mate choice, and also in the avoidance of predators, making it a vital sensory modality for preservation and reproduction. In the vertebrates, olfactory receptors are thought to localise on multiple cilia elaborated on the dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction can cause loss of the sense of smell, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a fork head-domain containing transcription factor traditionally linked with motile cilia biogenesis, is expressed in OSNs and required for olfactory epithelium formation. In keeping with the immotile nature of the olfactory cilia, we observed that ciliary motility genes that are the targets of Foxj1 in motile ciliated cells, are repressed in the OSNs. Strikingly, we also found that besides ciliogenesis, Foxj1 controls the differentiation of the OSNs by regulating their cell type-specific gene expression, such as that of olfactory marker protein (omp) involved in odour-evoked signal transduction. In line with these requirements, response to bile acid, an odour detected by OMP-positive OSNs, was significantly diminished in the foxj1 mutant zebrafish. Taken together, our findings establish how the canonical Foxj1-mediated motile ciliogenic transcriptional program has been repurposed for the biogenesis of the immotile olfactory cilia and for the development of the OSNs themselves.
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Project description:The simultaneous measurement of three-dimensional (3D) genome structure and gene expression of individual cells is critical for understanding our genome’s structure–function relation, yet is extremely challenging for existing methods. Here we present Linking mRNA to Chromatin Architecture (LiMCA), which jointly profiles 3D genome and transcriptome with exceptional sensitivity and from low-input materials. Combining LiMCA and our high-resolution scATAC-seq assay, METATAC, we profiled the developing mouse olfactory epithelium and reported the first chromatin accessibility profiles and the first paired 3D genome structures and gene expression information of single neurons. We greatly expanded the repertoire of known OR enhancers, and discovered unexpected rules of their dynamics: ORs and their enhancers are most accessible during early differentiation, and the active OR typically does not associate with the largest enhancer hub. These findings offer valuable insights into how 3D connectivity of ORs and enhancers dynamically orchestrate the “one neuron–one receptor” selection process.
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Project description:Individual olfactory sensory neurons (OSNs) express a single odorant receptor (OR) gene from the class I or class II repertoire in mice. The mechanisms that regulate the binary fate specification of OSNs remain unknown. Here we show that the transcription factor Bcl11b, which is expressed in class II OSNs determines the OR class to be expressed in OSNs. Genetic studies provide evidence that class I is a default-fate and Bcl11b permits a class II fate by suppressing a class I-OR enhancer. These findings reveal a unique transcriptional mechanism that serves as a binary switch to select the OR class and is crucial to both the anatomical and functional organization of olfactory system.
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Project description:Expression of one out of > 1000 olfactory receptor (OR) genes is stochastic, yet organized into anatomic "zones" along the dorsoventral axis of the olfactory epithelium. Here we profile the gene expression, chromatin state and nuclear architecture of olfactory sensory neurons and olfactory progenitors of different zones. We discovered that zonal OR expression is specified by two processes: low-level polygenic transcription of OR genes in olfactory progenitors, as wells as the chromatin structure and nuclear architecture during olfactory differentiation. Specifically, in cells of any zonal segment, polygenic transcription in olfactory progenitors defines the OR repertoire eligible for OR choice as the cells mature, while an increased level of heterochromatin and chromatin compaction represses ectopic more dorsally expressed ORs. We find that this process is regulated by the NFI family of transcription factors that are expressed in a graded fashion in the olfactory epithelium. Conditional deletion of NFI A, B, and X results in a transformation of the chromatin state and nucellar architecture and an accompanying shift in the preferred OR repertoire.
2023-06-14 | GSE158730 | GEO
Project description:The simultaneous measurement of three-dimensional (3D) genome structure and gene expression of individual cells is critical for understanding our genome’s structure–function relation, yet is extremely challenging for existing methods. Here we present Linking mRNA to Chromatin Architecture (LiMCA), which jointly profiles 3D genome and transcriptome with exceptional sensitivity and from low-input materials. Combining LiMCA and our high-resolution scATAC-seq assay, METATAC, we profiled the developing mouse olfactory epithelium and reported the first chromatin accessibility profiles and the first paired 3D genome structures and gene expression information of single neurons. We greatly expanded the repertoire of known OR enhancers, and discovered unexpected rules of their dynamics: ORs and their enhancers are most accessible during early differentiation, and the active OR typically does not associate with the largest enhancer hub. These findings offer valuable insights into how 3D connectivity of ORs and enhancers dynamically orchestrate the “one neuron–one receptor” selection process.
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Project description:The goal of RNA-seq is to explore whether olfactory sensory neurons (OSNs) that display a specific olfactory receptor (OR) express a distinct transcriptional program from OSNs that display a different OR. The GFP knockin mice (Olfr73-IRES-GFP, Olfr1507-IRES-GFP, and Olfr160-IRES-mCherry) was used to label the OSN expressing specific OR. These cells was then isolate with fluorescence activated cell sorting. For each sample, at least 5000 cells are collected, there biological replicates were collected for each genotype and in total 9 samples were prepared for RNA-seq libraries with using NEBNext® Single Cell/Low Input RNA Library Prep Kit for Illumina® (NEB) following the manufacturer’s guidelines with one alteration, which was to increase the insert length to ~300 base pair. Libraries were sequenced using paired end 150 cycle reads on an Illumina Hiseq4000 (Novogene). The sequencing reads were processed using the DolphinNext RNAseq pipeline (https://dolphinnext.umassmed.edu/index.php?np=1&id=732). The default settings were employed except STAR v2.6.1 and RSEM v1.3.1 were used for alignment and quantification, respectively. Differential analysis were conducted in DESeq2. The significant genes were deducted by computing Wald test with corrected p < 0.05. Our results shows that different types of OSNs express significantly different patterns of genes, especially the genes involved in axonal guidance.
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Project description:The overall aim of the experiment is to understand the phenotype of mature mouse olfactory sensory neurons by analyzing the transcripts expressed and enriched in them as compared to the rest of the cell types in the olfactory epithelium (consisting of immature neurons, supporting cells, progenitor cells and cells in lamina propria) and brain ( with out the olfactory bulbs). Comparision with the other cell types in the olfactory epithelium should eliminate the transcripts commonly expressed in the olfactory epithelium and comparision with brain will eliminate the transcripts common to most neurons. Our gene chip data indicates that mature mouse olfactory sensory neurons express 10,000 genes. Mature OSNs specifically contained three clusters of over represented Gene ontology categories: smell, ion transport and cilia. Analysis for the functionally over represented categories among the transcripts with a positive signal in the mature OSNs yielded largely broad categories common to all cells with the exception of chromatin modelling and RNA processing categories. Biological process categories of movement, development and immune response came as under represented categories. Experiment Overall Design: To purify mature olfactory neurons we took advantage of the OMP-GFP mice. OMP(olfactory marker protein) is expressed specifically in mature olfactory and vomeronasal sensory neurons. In the OMP-GFP mice the coding region of OMP is replaced by GFP. We purified OSNs from the rest of the epithelium from these mice by using FACS. . We used the Affymetrix gene chips mouse expression set 430 (consisting of 430A and 430B chips). Our gene chip data is extensively validated by insitu hybridizations.
2008-06-13 | E-GEOD-4915 | biostudies-arrayexpress