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

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

doi:10.1016/j.celrep.2022.110547

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

Cell Rep. 2022 Mar 22;38(12):110547. doi: 10.1016/j.celrep.2022.110547.

Authors

Mayra L Ruiz Tejada Segura¹, Eman Abou Moussa², Elisa Garabello³, Thiago S Nakahara⁴, Melanie Makhlouf², Lisa S Mathew², Li Wang², Filippo Valle⁵, Susie S Y Huang², Joel D Mainland⁶, Michele Caselle⁵, Matteo Osella⁵, Stephan Lorenz⁷, Johannes Reisert⁸, Darren W Logan⁹, Bettina Malnic⁴, Antonio Scialdone¹⁰, Luis R Saraiva¹¹

Affiliations

¹ Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, Feodor-Lynen-Strasse 21, 81377 München, Germany; Institute of Functional Epigenetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany; Institute of Computational Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
² Sidra Medicine, P.O. Box 26999, Doha, Qatar.
³ Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, Feodor-Lynen-Strasse 21, 81377 München, Germany; Physics Department, University of Turin and INFN, Via P. Giuria 1, 10125 Turin, Italy; Department of Civil and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.
⁴ Department of Biochemistry, University of São Paulo, São Paulo, Brazil.
⁵ Physics Department, University of Turin and INFN, Via P. Giuria 1, 10125 Turin, Italy.
⁶ Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁷ Sidra Medicine, P.O. Box 26999, Doha, Qatar; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
⁸ Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA.
⁹ Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
¹⁰ Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, Feodor-Lynen-Strasse 21, 81377 München, Germany; Institute of Functional Epigenetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany; Institute of Computational Biology, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany. Electronic address: antonio.scialdone@helmholtz-muenchen.de.
¹¹ Sidra Medicine, P.O. Box 26999, Doha, Qatar; Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA; College of Health and Life Sciences, Hamad Bin Khalifa University, P.O. Box 34110, Doha, Qatar. Electronic address: saraivalmr@gmail.com.

Abstract

The sense of smell helps us navigate the environment, but its molecular architecture and underlying logic remain understudied. The spatial location of odorant receptor genes (Olfrs) in the nose is thought to be independent of the structural diversity of the odorants they detect. Using spatial transcriptomics, we create a genome-wide 3D atlas of the mouse olfactory mucosa (OM). Topographic maps of genes differentially expressed in space reveal that both Olfrs and non-Olfrs are distributed in a continuous and overlapping fashion over at least five broad zones in the OM. The spatial locations of Olfrs correlate with the mucus solubility of the odorants they recognize, providing direct evidence for the chromatographic theory of olfaction. This resource resolves the molecular architecture of the mouse OM and will inform future studies on mechanisms underlying Olfr gene choice, axonal pathfinding, patterning of the nervous system, and basic logic for the peripheral representation of smell.

Keywords: CP: Neuroscience; RNA-seq; machine learning; odorant; olfaction; olfactory epithelium; olfactory mucosa; spatial transcriptomics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Logic
Mice
Odorants / analysis
Receptors, Odorant* / genetics
Smell* / genetics
Transcriptome / genetics

Substances

Receptors, Odorant

Grants and funding

R01 DC016647/DC/NIDCD NIH HHS/United States