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

Author

Listed:
  • Franziska Hildebrandt

    (Stockholm University)

  • Alma Andersson

    (KTH Royal Institute of Technology)

  • Sami Saarenpää

    (KTH Royal Institute of Technology)

  • Ludvig Larsson

    (KTH Royal Institute of Technology)

  • Noémi Van Hul

    (Karolinska Institutet Stockholm)

  • Sachie Kanatani

    (Stockholm University)

  • Jan Masek

    (Karolinska Institutet Stockholm
    Faculty of Science, Charles University)

  • Ewa Ellis

    (Intervention and Technology (CLINTEC), Karolinska Institutet)

  • Antonio Barragan

    (Stockholm University)

  • Annelie Mollbrink

    (KTH Royal Institute of Technology)

  • Emma R. Andersson

    (Karolinska Institutet Stockholm)

  • Joakim Lundeberg

    (KTH Royal Institute of Technology)

  • Johan Ankarklev

    (Stockholm University
    SciLifeLab, Biomedical Center (BMC) Uppsala University)

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 apply 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.

Suggested Citation

  • 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 L, 2021. "Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the mouse liver," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27354-w
    DOI: 10.1038/s41467-021-27354-w
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    Cited by:

    1. Wei Liu & Xu Liao & Ziye Luo & Yi Yang & Mai Chan Lau & Yuling Jiao & Xingjie Shi & Weiwei Zhai & Hongkai Ji & Joe Yeong & Jin Liu, 2023. "Probabilistic embedding, clustering, and alignment for integrating spatial transcriptomics data with PRECAST," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Franziska Hildebrandt & Miren Urrutia Iturritza & Christian Zwicker & Bavo Vanneste & Noémi Van Hul & Elisa Semle & Jaclyn Quin & Tales Pascini & Sami Saarenpää & Mengxiao He & Emma R. Andersson & Cha, 2024. "Host-pathogen interactions in the Plasmodium-infected mouse liver at spatial and single-cell resolution," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Haoyang Li & Juexiao Zhou & Zhongxiao Li & Siyuan Chen & Xingyu Liao & Bin Zhang & Ruochi Zhang & Yu Wang & Shiwei Sun & Xin Gao, 2023. "A comprehensive benchmarking with practical guidelines for cellular deconvolution of spatial transcriptomics," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    4. Francesca Lazzeri-Barcelo & Nuria Oliva-Vilarnau & Marion Baniol & Barbara Leibiger & Olaf Bergmann & Volker M. Lauschke & Ingo B. Leibiger & Noah Moruzzi & Per-Olof Berggren, 2024. "Intraocular liver spheroids for non-invasive high-resolution in vivo monitoring of liver cell function," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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