key: cord-0321201-547ineg8 authors: Diabasana, Zania; Perotin, Jeanne-Marie; Belgacemi, Randa; Ancel, Julien; Mulette, Pauline; Delepine, Gonzague; Gosset, Philippe; Maskos, Uwe; Polette, Myriam; Deslée, Gaëtan; Dormoy, Valérian title: Nicotinic receptors atlas in the adult human lung date: 2020-08-13 journal: bioRxiv DOI: 10.1101/2020.06.29.176750 sha: 64d7b22163228015a900cd8ade1307bdc1ebd2dc doc_id: 321201 cord_uid: 547ineg8 Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels responsible for the rapid neural and neuromuscular signal transmission. Although it is well documented that 16 subunits are encoded by the human genome, their presence in airway epithelial cells (AEC) remains poorly understood, and contribution to pathology is mainly discussed in the context of cancer. We analysed nAChR subunit expression in the human lung of smokers and non-smokers using transcriptomic data for whole lung tissues, isolated large AEC, and isolated small AEC. We identified differential expressions of nAChRs in terms of detection and repartition in the three modalities. Smoking-associated alterations were also unveiled. Then, we identified a nAChR transcriptomic print at a single cell level. Finally, we reported the localizations of detectable nAChRs in bronchi and large bronchioles. Thus, we compiled the first complete atlas of pulmonary nAChRs to open new avenues to further unravel the involvement of these receptors in lung homeostasis and respiratory diseases. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated (cation-permeable) 68 proteins expressed in the brain and in non-neuronal cells including lung AEC, macrophages, In the lung, acetylcholine binding to nAChR leads to an allosteric conformational 82 change permitting the channel opening, followed by ion fluxes that participate in cell survival, 83 differentiation, and proliferation [14, 15] . Nicotine, one of the components of cigarette smoke, 84 acts as an agonist implicated in the inhibition of apoptosis and oxidative stress responses 85 ultimately leading to lung impairments due to long-term exposure [5, 16, 17] . Previous studies 86 have established that multiple single nucleotide nAChR polymorphisms are respectively 87 associated with risks of lung cancer and chronic obstructive pulmonary disease (COPD), 88 highlighting their potential implication in respiratory diseases [14, 18, 19 ]. In addition, it has 89 been hypothesized that the nAChRs may play a role in coronavirus disease 2019 (COVID-19) 90 and might represent a therapeutic target, particularly regarding their potential contribution in The data are expressed as mean values and percentages. Differences between groups were 183 determined using the Student t test. A p-value <0.05 was considered significant. Smoking-associated pulmonary nAChRs subunits transcripts expressions 188 Considering the whole lung containing all types of tissues (Figure 1A) , the 16 nAChRs were 189 detected among non-smoker subjects except for CHRNA7, that was consistent in both 190 datasets containing non-smokers ( Figure 1B) . CHRNB1/E were very highly expressed; identity with regard to cross-reactivity (Supplemental Table S2 and S3, Supplemental 230 Figure S1 ). We focussed here on bronchi and large bronchioles as well as smooth muscle and 231 blood vessels on FFPE tissues (Figure 5A and B) . CHRNA1/A2/A4/B3/G were not detected. 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