Project description:How functional cellular heterogeneities are regulated is fundamental for understanding the molecular basis of complex organs. Olfactory sensory neurons (OSNs) are an ideal model to investigate the regulation of cellular heterogeneity. The “one-neuron-one-receptor” organization and topographical mapping ensure the detection and precise translation of odor signals to the central neural system. Besides the diversity of OR genes and other molecular guiding axon sorting processes, single-cell transcriptome analysis revealed an OSN subpopulation, defined by Cd36, a lipid receptor gene. The function study exhibited lipid odor identification was impaired in Cd36-deficient mice. In this study, we systematically depicted the transcriptome diversity, spatial distribution, and specific functions of Cd36+ OSNs in the mouse olfactory epithelium. The specific molecular features of Cd36+ OSN we revealed implemented the programmed cellular diversity may be driven by their olfaction function. Furthermore, with the integrative analysis of single-cell transcriptome and epigenome profiles, we revealed the cis and trans regulatory signatures in Cd36+ OSN and identified Tshz1 and Mef2 as the key regulators that may directly regulate and promote the expression of Cd36 and drive the cellular diversity of OSNs. Especially, we demonstrated that Tshz1 is expressed coordinately with the choices of ORs, earlier than the expression of Cd36, which indicates it may act as a pioneer factor that instructs the lineage-specific expression of Cd36 and other genes, eventually leading to the cellular diversity of Cd36+ OSN. Our results provide novel knowledge on the regulation mechanism of cellular diversity of complex organs.
Project description:How functional cellular heterogeneities are regulated is fundamental for understanding the molecular basis of complex organs. Olfactory sensory neurons (OSNs) are an ideal model to investigate the regulation of cellular heterogeneity. The “one-neuron-one-receptor” organization and topographical mapping ensure the detection and precise translation of odor signals to the central neural system. Besides the diversity of OR genes and other molecular guiding axon sorting processes, single-cell transcriptome analysis revealed an OSN subpopulation, defined by Cd36, a lipid receptor gene. The function study exhibited lipid odor identification was impaired in Cd36-deficient mice. In this study, we systematically depicted the transcriptome diversity, spatial distribution, and specific functions of Cd36+ OSNs in the mouse olfactory epithelium. The specific molecular features of Cd36+ OSN we revealed implemented the programmed cellular diversity may be driven by their olfaction function. Furthermore, with the integrative analysis of single-cell transcriptome and epigenome profiles, we revealed the cis and trans regulatory signatures in Cd36+ OSN and identified Tshz1 and Mef2 as the key regulators that may directly regulate and promote the expression of Cd36 and drive the cellular diversity of OSNs. Especially, we demonstrated that Tshz1 is expressed coordinately with the choices of ORs, earlier than the expression of Cd36, which indicates it may act as a pioneer factor that instructs the lineage-specific expression of Cd36 and other genes, eventually leading to the cellular diversity of Cd36+ OSN. Our results provide novel knowledge on the regulation mechanism of cellular diversity of complex organs.
Project description:Olfactory sensory neurons (OSNs) express a single abundant olfactory receptor (OR). To assess the differences in gene expression between different OSN sub-types we collected three pools of neurons that express one OR and compared them to three pools of neurons that express another. After extracting RNA from these pools, the samples were multiplexed and sequenced using the Illumina Hiseq2500 platform.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:Olfactory sensory neurons express just one out of a possible ~1000 odorant receptor genes, reflecting an exquisite mode of gene regulation. In one model, once an odorant receptor is chosen for expression, other receptor genes are suppressed by a negative feedback mechanism, ensuring a stable functional identity of the sensory neuron for the lifetime of the cell. The signal transduction mechanism subserving odorant receptor gene silencing remains obscure, however. Here we demonstrate in the zebrafish that odorant receptor gene silencing is dependent on receptor activity. Moreover, we show that signaling through G protein M-NM-2M-NM-3 subunits is both necessary and sufficient to suppress the expression of odorant receptor genes, and likely acts through histone methylation to maintain the silenced odorant receptor genes in transcriptionally inactive heterochromatin. These results provide new insights linking receptor activity with the epigenetic mechanisms responsible for ensuring the expression of one odorant receptor per olfactory sensory neuron. Total 6 samples were analyzed-3 controls & 3 samples
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.