Spatial tissue profiling by imaging-free molecular tomography

Halima Hannah Schede1, Christian G Schneider1,2, Johanna Stergiadou3,4, Lars E Borm3, Anurag Ranjak1, Tracy M Yamawaki5,6, Fabrice P A David1,7, Peter Lönnerberg3, Maria Antonietta Tosches5,8, Simone Codeluppi3, Gioele La Manno9

  1. Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  2. Charité-Universitätsmedizin Berlin, corporate member of the Freie Universität Berlin and Humboldt-Universität zu Berlin: NeuroCure Clinical Research Center, Berlin, Germany.
  3. Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
  4. 10x Genomics, Stockholm, Sweden.
  5. Max Planck Institute for Brain Research, Frankfurt am Main, Germany.
  6. Amgen, Inc., South San Francisco, CA, USA.
  7. BioInformatics Competence Center, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  8. Department of Biological Sciences, Columbia University, New York, NY, USA.
  9. Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. gioele.lamanno@epfl.ch.

Abstract

Several techniques are currently being developed for spatially resolved omics profiling, but each new method requires the setup of specific detection strategies or specialized instrumentation. Here we describe an imaging-free framework to localize high-throughput readouts within a tissue by cutting the sample into thin strips in a way that allows subsequent image reconstruction. We implemented this framework to transform a low-input RNA sequencing protocol into an imaging-free spatial transcriptomics technique (called STRP-seq) and validated it by profiling the spatial transcriptome of the mouse brain. We applied the technique to the brain of the Australian bearded dragon, Pogona vitticeps. Our results reveal the molecular anatomy of the telencephalon of this lizard, providing evidence for a marked regionalization of the reptilian pallium and subpallium. We expect that STRP-seq can be used to derive spatially resolved data from a range of other omics techniques.

Presented By Halima Schede, Christian Schneider