Effects of olfactory-specific Bcl11b overexpression on gene expression in the main olfactory epithelium of neonatal mice.
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ABSTRACT:
PROVIDER: PRJNA484758 | ENA |
REPOSITORIES: ENA
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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:Each olfactory sensory neuron (OSN) chooses a single odorant receptor (OR) gene from the class I or class II OR repertoire in mice. We have found that the transcription factor Bcl11b, which is coexpressed with class II OR genes both in frog and mouse, determines the class of OR to be expressed in OSNs. Both loss- and gain-of-function analyses demonstrate that Bcl11b is necessary for class II genes expression, by suppressing the class I-specific enhancer. Overall, we identified a unique transcriptional mechanism that serves as a binary switch for the OR class choice that is likely to have contributed to the acquisition of terrestrial-specific class II OR expression.
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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).
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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).
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Project description:The goal of scRNA-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 in a large and unbias scale. Olfactory epithelial single cell suspensions were made using 3 male and 3 female mice. Single-cell sequencing libraries were prepared using Chromium Single Cell 3’ Reagent Kit V3 (10X Genomics) according to the manufacturer’s guidelines. Libraries were sequenced using 150 cycles of paired end reads on Illumina Hiseq4000 and Novaseq6000 instruments (Novogene). The sequencing reads were processed using the DolphinNext Single Cell-10X Genomics pipeline (https://dolphinnext.umassmed.edu/index.php?np=1&id=420, default settings except STAR v2.6.1 was used for alignment).
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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.
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2011-05-27 | GSE26064 | GEO
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.
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