IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-27354-w.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27354-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-27354-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Sonya A. MacParland & Jeff C. Liu & Xue-Zhong Ma & Brendan T. Innes & Agata M. Bartczak & Blair K. Gage & Justin Manuel & Nicholas Khuu & Juan Echeverri & Ivan Linares & Rahul Gupta & Michael L. Cheng, 2018. "Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations," Nature Communications, Nature, vol. 9(1), pages 1-21, December.
    2. Keren Bahar Halpern & Rom Shenhav & Orit Matcovitch-Natan & Beáta Tóth & Doron Lemze & Matan Golan & Efi E. Massasa & Shaked Baydatch & Shanie Landen & Andreas E. Moor & Alexander Brandis & Amir Gilad, 2017. "Single-cell spatial reconstruction reveals global division of labour in the mammalian liver," Nature, Nature, vol. 542(7641), pages 352-356, February.
    3. Nadim Aizarani & Antonio Saviano & Sagar & Laurent Mailly & Sarah Durand & Josip S. Herman & Patrick Pessaux & Thomas F. Baumert & Dominic Grün, 2019. "A human liver cell atlas reveals heterogeneity and epithelial progenitors," Nature, Nature, vol. 572(7768), pages 199-204, August.
    4. Charlotte L. Scott & Fang Zheng & Patrick De Baetselier & Liesbet Martens & Yvan Saeys & Sofie De Prijck & Saskia Lippens & Chloé Abels & Steve Schoonooghe & Geert Raes & Nick Devoogdt & Bart N. Lambr, 2016. "Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    5. Keren Bahar Halpern & Rom Shenhav & Orit Matcovitch-Natan & Beáta Tóth & Doron Lemze & Matan Golan & Efi E. Massasa & Shaked Baydatch & Shanie Landen & Andreas E. Moor & Alexander Brandis & Amir Gilad, 2017. "Erratum: Single-cell spatial reconstruction reveals global division of labour in the mammalian liver," Nature, Nature, vol. 543(7647), pages 742-742, March.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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. 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.
    3. 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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Inmaculada Ruz-Maldonado & John T. Gonzalez & Hanming Zhang & Jonathan Sun & Alicia Bort & Inamul Kabir & Richard G. Kibbey & Yajaira Suárez & Daniel M. Greif & Carlos Fernández-Hernando, 2024. "Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    2. Jie Fang & Shivendra Singh & Changde Cheng & Sivaraman Natarajan & Heather Sheppard & Ahmed Abu-Zaid & Adam D. Durbin & Ha Won Lee & Qiong Wu & Jacob Steele & Jon P. Connelly & Hongjian Jin & Wenan Ch, 2023. "Genome-wide mapping of cancer dependency genes and genetic modifiers of chemotherapy in high-risk hepatoblastoma," Nature Communications, Nature, vol. 14(1), pages 1-27, December.
    3. Ana Belén Plata-Gómez & Lucía Prado-Rivas & Alba Sanz & Nerea Deleyto-Seldas & Fernando García & Celia Calle Arregui & Camila Silva & Eduardo Caleiras & Osvaldo Graña-Castro & Elena Piñeiro-Yáñez & Jo, 2024. "Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Zhiyuan Yuan & Yisi Li & Minglei Shi & Fan Yang & Juntao Gao & Jianhua Yao & Michael Q. Zhang, 2022. "SOTIP is a versatile method for microenvironment modeling with spatial omics data," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    5. Jingyang Qian & Jie Liao & Ziqi Liu & Ying Chi & Yin Fang & Yanrong Zheng & Xin Shao & Bingqi Liu & Yongjin Cui & Wenbo Guo & Yining Hu & Hudong Bao & Penghui Yang & Qian Chen & Mingxiao Li & Bing Zha, 2023. "Reconstruction of the cell pseudo-space from single-cell RNA sequencing data with scSpace," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Kristina Handler & Karsten Bach & Costanza Borrelli & Salvatore Piscuoglio & Xenia Ficht & Ilhan E. Acar & Andreas E. Moor, 2023. "Fragment-sequencing unveils local tissue microenvironments at single-cell resolution," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Sun Woo Sophie Kang & Rory P. Cunningham & Colin B. Miller & Lauryn A. Brown & Constance M. Cultraro & Adam Harned & Kedar Narayan & Jonathan Hernandez & Lisa M. Jenkins & Alexei Lobanov & Maggie Cam , 2024. "A spatial map of hepatic mitochondria uncovers functional heterogeneity shaped by nutrient-sensing signaling," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. T. Hautz & S. Salcher & M. Fodor & G. Sturm & S. Ebner & A. Mair & M. Trebo & G. Untergasser & S. Sopper & B. Cardini & A. Martowicz & J. Hofmann & S. Daum & M. Kalb & T. Resch & F. Krendl & A. Weisse, 2023. "Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Zoe Piran & Mor Nitzan, 2024. "SiFT: uncovering hidden biological processes by probabilistic filtering of single-cell data," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Lei Xiong & Kang Tian & Yuzhe Li & Weixi Ning & Xin Gao & Qiangfeng Cliff Zhang, 2022. "Online single-cell data integration through projecting heterogeneous datasets into a common cell-embedding space," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    11. Ting Dong & Guangan Hu & Zhongqi Fan & Huirui Wang & Yinghui Gao & Sisi Wang & Hao Xu & Michael B. Yaffe & Matthew G. Vander Heiden & Guoyue Lv & Jianzhu Chen, 2024. "Activation of GPR3-β-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    12. Manuel Neumann & Xiaocai Xu & Cezary Smaczniak & Julia Schumacher & Wenhao Yan & Nils Blüthgen & Thomas Greb & Henrik Jönsson & Jan Traas & Kerstin Kaufmann & Jose M. Muino, 2022. "A 3D gene expression atlas of the floral meristem based on spatial reconstruction of single nucleus RNA sequencing data," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    13. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    14. Yuan Guan & Annika Enejder & Meiyue Wang & Zhuoqing Fang & Lu Cui & Shih-Yu Chen & Jingxiao Wang & Yalun Tan & Manhong Wu & Xinyu Chen & Patrik K. Johansson & Issra Osman & Koshi Kunimoto & Pierre Rus, 2021. "A human multi-lineage hepatic organoid model for liver fibrosis," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    15. 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.
    16. James T. Topham & Erica S. Tsang & Joanna M. Karasinska & Andrew Metcalfe & Hassan Ali & Steve E. Kalloger & Veronika Csizmok & Laura M. Williamson & Emma Titmuss & Karina Nielsen & Gian Luca Negri & , 2022. "Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    17. Aleksandr Ianevski & Anil K. Giri & Tero Aittokallio, 2022. "Fully-automated and ultra-fast cell-type identification using specific marker combinations from single-cell transcriptomic data," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    18. Shanshan Guo & Yonghao Feng & Xiaopeng Zhu & Xinyi Zhang & Hui Wang & Ruwen Wang & Qiongyue Zhang & Yiming Li & Yan Ren & Xin Gao & Hua Bian & Tiemin Liu & Huanqing Gao & Xingxing Kong, 2023. "Metabolic crosstalk between skeletal muscle cells and liver through IRF4-FSTL1 in nonalcoholic steatohepatitis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Sarah Cappuyns & Gino Philips & Vincent Vandecaveye & Bram Boeckx & Rogier Schepers & Thomas Van Brussel & Ingrid Arijs & Aurelie Mechels & Ayse Bassez & Francesca Lodi & Joris Jaekers & Halit Topal &, 2023. "PD-1- CD45RA+ effector-memory CD8 T cells and CXCL10+ macrophages are associated with response to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    20. Joachim Jonghe & Tomasz S. Kaminski & David B. Morse & Marcin Tabaka & Anna L. Ellermann & Timo N. Kohler & Gianluca Amadei & Charlotte E. Handford & Gregory M. Findlay & Magdalena Zernicka-Goetz & Sa, 2023. "spinDrop: a droplet microfluidic platform to maximise single-cell sequencing information content," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27354-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.