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Transcriptional adaptation of olfactory sensory neurons to GPCR identity and activity [MOR23]

ABSTRACT: In mammals, chemoperception relies on a diverse set of neuronal sensors able to detect chemicals present in the environment, and to adapt to various levels of stimulation. The contribution of endogenous and external factors to these neuronal identities remains to be determined. Taking advantage of the extensive parallel coding lines present in the olfactory system, we explored the potential variations of neuronal identities before and after olfactory experience. We found that at rest, the transcriptomic profiles of mouse olfactory sensory neuron populations are already highly divergent, specific to the olfactory receptor they express, and are surprisingly associated with the sequence of these latter. These divergent profiles further evolve in response to the environment, as odorant exposure leads to massive reprogramming via the modulation of transcription. These findings highlight a broad range of sensory neuron identities that are present at rest and that adapt to the experience of the individual, thus adding to the complexity and flexibility of sensory coding.

ORGANISM(S): Mus musculus

PROVIDER: GSE185167 | GEO | 2022/05/02

REPOSITORIES: GEO

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Transcriptional adaptation of olfactory sensory neurons to GPCR identity and activity [M71]

Project description:In mammals, chemoperception relies on a diverse set of neuronal sensors able to detect chemicals present in the environment, and to adapt to various levels of stimulation. The contribution of endogenous and external factors to these neuronal identities remains to be determined. Taking advantage of the extensive parallel coding lines present in the olfactory system, we explored the potential variations of neuronal identities before and after olfactory experience. We found that at rest, the transcriptomic profiles of mouse olfactory sensory neuron populations are already highly divergent, specific to the olfactory receptor they express, and are surprisingly associated with the sequence of these latter. These divergent profiles further evolve in response to the environment, as odorant exposure leads to massive reprogramming via the modulation of transcription. These findings highlight a broad range of sensory neuron identities that are present at rest and that adapt to the experience of the individual, thus adding to the complexity and flexibility of sensory coding.

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Genome-wide location analysis of FLAG-H2BE

Project description:We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment. The objective of generating this dataset was to analyze the occupancy of H2BE protein in the vicinity of gene promoters throughout the genome, relative to histone H3, in olfactory sensory neurons within the main olfactory epithelium (MOE). This dataset analyzes the occupancy of FLAG-H2BE protein in the vicinity of gene promoters throughout the genome, relative to histone H3, in olfactory sensory neurons within the main olfactory epithelium (MOE) of Flag-H2be transgenic mice, which express a FLAG-tagged version of H2BE from the H2be promoter. There are 2 replicates for each ChIP (FLAG and H3).

2012-09-01 | E-GEOD-39517 | biostudies-arrayexpress

Effects of H2be loss of function on gene expression in the main olfactory epithelium (MOE) of 6-month old mice.

Project description:We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment. The objective of generating this dataset was to analyze the effects of H2be loss of function on gene expression in the main olfactory epithelium of 6-month old mice. This dataset compares gene expression in wild type and H2be-KO main olfactory epithelium (MOE) samples. There are six replicates for each genotype (equal mixture of males and females).

2012-09-01 | E-GEOD-39515 | biostudies-arrayexpress

Genome-wide location analysis of FLAG-H2BE

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Effects of H2be ectopic over-expression on gene expression in the main olfactory epithelium (MOE) of 5-week old mice.

Project description:We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment. The objective of generating this dataset was to analyze the effects of the ectopic over-expression of H2be (expressed from an Omp-promoter-driven transgene and tagged with a FLAG epitope) on gene expression in the main olfactory epithelium of 5-week old mice. This dataset compares gene expression in wild type and H2be-GF main olfactory epithelium (MOE) samples. There are 6 replicates for WT and 4 replicates for H2be-GF (equal mixture of males and females).

2012-09-01 | E-GEOD-39514 | biostudies-arrayexpress

Effects of H2be loss of function on gene expression changes in the main olfactory epithelium (MOE) as a result of activity deprivation through unilateral naris occlusion (UNO).

Project description:We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment. The objective of generating this dataset was to analyze the effects of H2be loss of function on gene expression changes in the main olfactory epithelium as a result of activity deprivation through unilateral naris occlusion (UNO).

2012-09-01 | GSE39516 | GEO

Effects of H2be loss of function on gene expression in the main olfactory epithelium (MOE) of 6-month old mice.

2012-09-01 | GSE39515 | GEO

Effects of H2be loss of function on gene expression changes in the main olfactory epithelium (MOE) as a result of activity deprivation through unilateral naris occlusion (UNO).

Project description:We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment. The objective of generating this dataset was to analyze the effects of H2be loss of function on gene expression changes in the main olfactory epithelium as a result of activity deprivation through unilateral naris occlusion (UNO). This dataset compares gene expression in wild type and H2be-KO main olfactory epithelium (MOE) samples from 5-week old mice that were subjected to unilateral naris occlusion (UNO) for 3 weeks starting from 2 weeks of age. Samples consist of MOE halves that were dissected and carefully removed from the medial bone. Each sample contains tissue from 2 mice (1 female and 1 male). There are three replicates for each genotype (H2be-KO or WT) and UNO side (open or closed) combination.

2012-09-01 | E-GEOD-39516 | biostudies-arrayexpress

A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity

Project description:Sensory neuron diversity is required for organisms to decipher complex environmental cues. In Drosophila, olfactory environment is detected by 50 different olfactory receptor neuron (ORN) classes that are clustered in combinations within distinct sensilla subtypes. Each sensilla subtype houses stereotypically clustered 1-4 ORN identities that arise through asymmetric divisions from a single multipotent sensory organ precursor (SOP). How each class of SOPs acquires a unique differentiation potential that accounts for ORN diversity is unknown. Previously, we reported a critical component of SOP diversification program, Rotund (Rn), which functions to increase ORN diversity by generating novel developmental trajectories from existing precursors within each independent sensilla type lineages. Here, we show that Rn, along with BarH1/H2, Bric-Ã -brac (Bab), Apterous (Ap) and Dachshund (Dac), constitute a functionally conserved transcription factor (TF) network, previously shown to pattern the segmentation of the leg, that patterns the developing olfactory tissue. Precursors with diverse ORN differentiation potentials are selected from concentric rings defined by unique combinations of these TFs along the proximodistal axis of the developing antennal disc. The combinatorial code that demarcates each precursor field is set up by cross-regulatory interactions among different factors within the network. Modifications of this network lead to predictable changes in the diversity of sensilla subtypes and ORN pools. In light of our data, we propose a molecular map that defines Time-course RNAseq across 4 developmental stages, inlcuding flies mutant for rotund gene (rn), heterozygotes and wildtype

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