A 3D transcriptomics atlas of the mouse nose sheds light on the anatomical logic of smell

Segura, Mayra L. Ruiz Tejada; Moussa, Eman Abou; Garabello, Elisa; Nakahara, Thiago Seike; Makhlouf, Mélanie; Mathew, Lisa S.; Wang, Li; Valle, Filippo; Huang, Shengshu; Mainland, Joel D.; Caselle, Michele; Osella, Matteo; Lorenz, Stephan; Reisert, Johannes; Logan, Darren W.; Malnic, Bettina; Scialdone, Antonio; Saraiva, Luís R.

doi:10.1016/j.celrep.2022.110547

Cited by 20 publications

(18 citation statements)

References 159 publications

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“…Recent RNA-seq studies in the mammalian WOM have demonstrated that this high-throughput technology is highly reliable in quantifying the abundance of thousands of OSN subtypes, based on the chemosensory receptor (e.g., OR, TAAR) they express (Ibarra-Soria et al, 2017; Ruiz Tejada Segura et al, 2022; Saraiva et al, 2015; Saraiva et al, 2019). In the 5×21-OR1A1 mouse line approximately 13% of all OSNs express OR1A1 (based on glomerular volume).…”

Section: Resultsmentioning

confidence: 99%

“…Cell type restriction is a mechanism that seems likely to group OR functionality to the same projection sites in the bulb (Figure S5). In this regard, grouping odor receptive properties of ORs may be a mechanism to more accurately characterize the nature of a stimulus, consistent with the fact that the spatial location of ORs correlate with sorption patterns of the odorants they recognize (Ruiz Tejada Segura et al, 2022). Therefore, cell type restriction would not necessarily be a means to reduce the repertoire of OR genes an OSN can chose from in order to reduce the complexity governing the process of singular gene choice.…”

Section: Cell Type Restriction Of Orsmentioning

confidence: 95%

“…A study combining regional dissections of random small pieces of the MOE coupled with RNA-sequencing (RNA-seq) mapped 1,033 mouse ORs and seven TAARs to 39 distinct dorsal to ventral (DV) regions (Zone Indexes 1.05 to 5.0) and an "unusual location" (patch zone) (Tan and Xie, 2018). Similarly, another recent study using a spatial transcriptomics approach created a genome-wide 3D atlas of the mouse whole olfactory mucosa (WOM) and found that ORs are distributed in a continuous fashion over five epithelial regions (Ruiz Tejada Segura et al, 2022). In contrast, another study combining in situ hybridization of approximately 70 OR genes with wholemount 3D reconstructions, suggested that the minimum number of OR zones is nine (Zapiec and Mombaerts, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Commonality of Odorant Receptor Choice Mechanism Revealed by Analysis of a Highly Represented Odorant Receptor Transgene

Makhlouf

D’Hulst

Omura

et al. 2022

Preprint

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In the mouse, more than 1,100 odorant receptors (ORs) are expressed in a monogenic and monoallelic fashion, referred to as singular gene expression. Using a 21bp singular-choice enhancer (x21), we radically increase representation of olfactory sensory neurons (OSNs) choosing a 5x21 enhanced OR transgene, but not overexpression of its mRNA on a per cell basis. RNA-sequencing and differential expression analysis identified 425 differentially expressed genes (DEGs). ORs make up 86% of all DEGs, of which 325 have decreased representation and 40 have increased representation. Underrepresented ORs include Class I, Class II and TAAR genes and within each of their respective olfactory bulb domains: DI, DII, and DIII (TAAR) we committedly observe multiple homogeneous glomeruli with an OR1A1-identity. The underrepresentation of endogenous, class-specific ORs across evolutionarily distinct cell types in favor of the expression of the 5x21-OR1A1 transgene argues that a common mechanism of singular gene choice is present for all OR-expressing OSNs.

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Section: Resultsmentioning

confidence: 99%

Section: Cell Type Restriction Of Orsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Commonality of Odorant Receptor Choice Mechanism Revealed by Analysis of a Highly Represented Odorant Receptor Transgene

Makhlouf

D’Hulst

Omura

et al. 2022

Preprint

Self Cite

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“…Each individual mature OSN expresses just one allele of one OR, selecting from a family of over 1100 OR genes [1][2][3][4][5]. OSNs expressing the same OR, known as 'like-OSNs', are not spatially clustered in the OE but are instead distributed in salt-and-pepper, interspersed patterns within a range of complex and overlapping nasal expression zones [6][7][8][9]. While some broad spatial organization is present in the way that these expression zones send projections to central targets (see §3), the most striking feature of the nose-to-brain map is the extreme local precision of like-OSN axonal targeting.…”

Section: Introductionmentioning

confidence: 99%

Developing and maintaining a nose-to-brain map of odorant identity

Dorrego-Rivas

Grubb

2022

Open Biol.

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Olfactory sensory neurons (OSNs) in the olfactory epithelium of the nose transduce chemical odorant stimuli into electrical signals. These signals are then sent to the OSNs' target structure in the brain, the main olfactory bulb (OB), which performs the initial stages of sensory processing in olfaction. The projection of OSNs to the OB is highly organized in a chemospatial map, whereby axon terminals from OSNs expressing the same odorant receptor (OR) coalesce into individual spherical structures known as glomeruli. This nose-to-brain map of odorant identity is built from late embryonic development to early postnatal life, through a complex combination of genetically encoded, OR-dependent and activity-dependent mechanisms. It must then be actively maintained throughout adulthood as OSNs experience turnover due to external insult and ongoing neurogenesis. Our review describes and discusses these two distinct and crucial processes in olfaction, focusing on the known mechanisms that first establish and then maintain chemospatial order in the mammalian OSN-to-OB projection.

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“…To capture the heterogeneity of lncRNA expression at single cell level, we used a new clustering approach called topic modeling (10)(11)(12), a method originally designed to analyse the words in a corpus of text documents to discover the themes, or topics, that pervade them. Through an analogy between document analysis and single-cell analysis and guided by the fact that similar statistical laws emerge in both of these contexts (13), we applied topic modeling to discover the protein coding genes and the lncRNAs that group thousands of cells into biologically similar clusters.…”

Section: Introductionmentioning

confidence: 99%

Identification of interpretable clusters and associated signatures in breast cancer single cell data: a topic modeling approach

Malagoli

Valle

Barillot

et al. 2022

Preprint

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Single-cell RNA sequencing is a powerful tool to explore cancer heterogeneity. However, the expression of lncRNAs in single cells is still to be studied extensively and methods to deal with the sparsity of this type of data are lacking. Here, we propose a topic modeling approach to investigate the transcriptional heterogeneity of luminal and triple negative breast cancer cells using patient-derived xenograft models of acquired resistance to chemotherapy and targeted therapy. We show that using an integrative clustering that combines the information coming from mRNAs and lncRNAs treated as disjoint omic layers greatly improves the accuracy of cell classification. Topics associated with specific breast cancer subpopulations show a clear enrichment for pathways involved in subtyping and progression of breast cancer and to sets of lncRNA encoded in the open chromatin regions of breast cancer cell lines. We identified lncRNAs strongly associated with cell clusters already well known in the literature, such as MALAT1 and NEAT1, and highlighted some others that may be clinically relevant.

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A 3D transcriptomics atlas of the mouse nose sheds light on the anatomical logic of smell

Cited by 20 publications

References 159 publications

Commonality of Odorant Receptor Choice Mechanism Revealed by Analysis of a Highly Represented Odorant Receptor Transgene

Commonality of Odorant Receptor Choice Mechanism Revealed by Analysis of a Highly Represented Odorant Receptor Transgene

Developing and maintaining a nose-to-brain map of odorant identity

Identification of interpretable clusters and associated signatures in breast cancer single cell data: a topic modeling approach

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