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Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the liver

View ORCID ProfileFranziska Hildebrandt, Alma Andersson, View ORCID ProfileSami Saarenpää, View ORCID ProfileLudvig Larsson, Noémi Van Hul, View ORCID ProfileSachie Kanatani, Jan Masek, View ORCID ProfileEwa Ellis, View ORCID ProfileAntonio Barragan, View ORCID ProfileAnnelie Mollbrink, View ORCID ProfileEmma R. Andersson, View ORCID ProfileJoakim Lundeberg, View ORCID ProfileJohan Ankarklev
doi: https://doi.org/10.1101/2021.01.11.426100
Franziska Hildebrandt
1Molecular Biosciences, the Wenner Gren Institute, Stockholm University, Svante Arrhenius Väg 20C, SE-106 91 Stockholm, Sweden
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  • For correspondence: franziska.hildebrandt@su.se johan.ankarklev@su.se
Alma Andersson
2Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Tomtebodavägen 23a, SE-171 65, Solna, Sweden
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Sami Saarenpää
2Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Tomtebodavägen 23a, SE-171 65, Solna, Sweden
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Ludvig Larsson
2Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Tomtebodavägen 23a, SE-171 65, Solna, Sweden
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Noémi Van Hul
3Department of Cell and Molecular Biology, Karolinska Institutet Stockholm, SE-171 77, Solna, Sweden
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Sachie Kanatani
1Molecular Biosciences, the Wenner Gren Institute, Stockholm University, Svante Arrhenius Väg 20C, SE-106 91 Stockholm, Sweden
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Jan Masek
3Department of Cell and Molecular Biology, Karolinska Institutet Stockholm, SE-171 77, Solna, Sweden
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Ewa Ellis
4Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, 141-86, Stockholm, Sweden
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Antonio Barragan
1Molecular Biosciences, the Wenner Gren Institute, Stockholm University, Svante Arrhenius Väg 20C, SE-106 91 Stockholm, Sweden
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Annelie Mollbrink
2Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Tomtebodavägen 23a, SE-171 65, Solna, Sweden
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Emma R. Andersson
3Department of Cell and Molecular Biology, Karolinska Institutet Stockholm, SE-171 77, Solna, Sweden
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Joakim Lundeberg
2Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Tomtebodavägen 23a, SE-171 65, Solna, Sweden
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Johan Ankarklev
1Molecular Biosciences, the Wenner Gren Institute, Stockholm University, Svante Arrhenius Väg 20C, SE-106 91 Stockholm, Sweden
5Microbial Single Cell Genomics facility, Science for Life Laboratory, Biomedical Center (BMC) Uppsala University, SE-751 23, Uppsala, Sweden
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  • For correspondence: franziska.hildebrandt@su.se johan.ankarklev@su.se
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ABSTRACT

Reconstruction of heterogeneity through single-cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we implement Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://zenodo.org/record/4399655

  • https://github.com/almaan/ST-mLiver

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 12, 2021.
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Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the liver
Franziska Hildebrandt, Alma Andersson, Sami Saarenpää, Ludvig Larsson, Noémi Van Hul, Sachie Kanatani, Jan Masek, Ewa Ellis, Antonio Barragan, Annelie Mollbrink, Emma R. Andersson, Joakim Lundeberg, Johan Ankarklev
bioRxiv 2021.01.11.426100; doi: https://doi.org/10.1101/2021.01.11.426100
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Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the liver
Franziska Hildebrandt, Alma Andersson, Sami Saarenpää, Ludvig Larsson, Noémi Van Hul, Sachie Kanatani, Jan Masek, Ewa Ellis, Antonio Barragan, Annelie Mollbrink, Emma R. Andersson, Joakim Lundeberg, Johan Ankarklev
bioRxiv 2021.01.11.426100; doi: https://doi.org/10.1101/2021.01.11.426100

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