staff

Joël Tuberosa

Postdoctoral fellow in Neurogenetics

  • T: +41 22 379 32 81
  • office 4031a (Sciences III)
  • Transcriptional adaptation of olfactory sensory neurons to GPCR identity and activity. Nat Commun 2022 May;13(1):2929. 10.1038/s41467-022-30511-4. 10.1038/s41467-022-30511-4.

    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 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 divergent, specific to the olfactory receptor they express, and are associated with the sequence of these latter. These divergent profiles further evolve in response to the environment, as odorant exposure leads to 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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  • SARS-CoV-2 receptors and entry genes are expressed in the human olfactory neuroepithelium and brain. iScience 2020 Nov;():101839. 10.1016/j.isci.2020.101839. S2589-0042(20)31036-1. PMC7685946.

    abstract

    Reports indicate an association between COVID-19 and anosmia, as well as the presence of SARS-CoV-2 virions in the olfactory bulb. To test whether the olfactory neuroepithelium may represent a target of the virus, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2), and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express and . ACE2 protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.

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  • Evolution of immune chemoreceptors into sensors of the outside world. Proc. Natl. Acad. Sci. U.S.A. 2017 Jun;():. 1704009114. 10.1073/pnas.1704009114.

    abstract

    Changes in gene expression patterns represent an essential source of evolutionary innovation. A striking case of neofunctionalization is the acquisition of neuronal specificity by immune formyl peptide receptors (Fprs). In mammals, Fprs are expressed by immune cells, where they detect pathogenic and inflammatory chemical cues. In rodents, these receptors are also expressed by sensory neurons of the vomeronasal organ, an olfactory structure mediating innate avoidance behaviors. Here we show that two gene shuffling events led to two independent acquisitions of neuronal specificity by Fprs. The first event targeted the promoter of a V1R receptor gene. This was followed some 30 million years later by a second genomic accident targeting the promoter of a V2R gene. Finally, we show that expression of a vomeronasal Fpr can reverse back to the immune system under inflammatory conditions via the production of an intergenic transcript linking neuronal and immune Fpr genes. Thus, three hijackings of regulatory elements are sufficient to explain all aspects of the complex expression patterns acquired by a receptor family that switched from sensing pathogens inside the organism to sensing the outside world through the nose.

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  • Large-scale transcriptional profiling of chemosensory neurons identifies receptor-ligand pairs in vivo. Nat. Neurosci. 2015 Oct;18(10):1455-63. nn.4100. 10.1038/nn.4100.

    abstract

    In mammals, olfactory perception is based on the combinatorial activation of G protein-coupled receptors. Identifying the full repertoire of receptors activated by a given odorant in vivo, a quest that has been hampered for over 20 years by technical difficulties, would represent an important step in deciphering the rules governing chemoperception. We found that odorants induced a fast and reversible concentration-dependent decrease in the transcription of genes corresponding to activated receptors in intact mice. On the basis of this finding, we developed a large-scale transcriptomic approach to uncover receptor-ligand pairs in vivo. We identified the mouse and rat odorant receptor signatures corresponding to specific odorants. Finally, we found that this approach, which can be used for species for which no genomic sequence is available, is also applicable to non-vertebrate species such as Drosophila.

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