IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43201-6.html
   My bibliography  Save this article

High-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq

Author

Listed:
  • Jasim Kada Benotmane

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg)

  • Jan Kueckelhaus

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg)

  • Paulina Will

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg)

  • Junyi Zhang

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg)

  • Vidhya M. Ravi

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg
    Translational NeuroOncology Research Group, Medical Center—University of Freiburg)

  • Kevin Joseph

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg
    Translational NeuroOncology Research Group, Medical Center—University of Freiburg)

  • Roman Sankowski

    (Medical Center—University of Freiburg)

  • Jürgen Beck

    (Medical Center - University of Freiburg
    Freiburg University)

  • Catalina Lee-Chang

    (Northwestern University Feinberg School of Medicine)

  • Oliver Schnell

    (Medical Center - University of Freiburg
    Freiburg University
    Translational NeuroOncology Research Group, Medical Center—University of Freiburg)

  • Dieter Henrik Heiland

    (Medical Center - University of Freiburg
    Freiburg University
    Medical Center—University of Freiburg
    Northwestern University Feinberg School of Medicine)

Abstract

Spatial resolution of the T cell repertoire is essential for deciphering cancer-associated immune dysfunction. Current spatially resolved transcriptomic technologies are unable to directly annotate T cell receptors (TCR). We present spatially resolved T cell receptor sequencing (SPTCR-seq), which integrates optimized target enrichment and long-read sequencing for highly sensitive TCR sequencing. The SPTCR computational pipeline achieves yield and coverage per TCR comparable to alternative single-cell TCR technologies. Our comparison of PCR-based and SPTCR-seq methods underscores SPTCR-seq’s superior ability to reconstruct the entire TCR architecture, including V, D, J regions and the complementarity-determining region 3 (CDR3). Employing SPTCR-seq, we assess local T cell diversity and clonal expansion across spatially discrete niches. Exploration of the reciprocal interaction of the tumor microenvironmental and T cells discloses the critical involvement of NK and B cells in T cell exhaustion. Integrating spatially resolved omics and TCR sequencing provides as a robust tool for exploring T cell dysfunction in cancers and beyond.

Suggested Citation

  • Jasim Kada Benotmane & Jan Kueckelhaus & Paulina Will & Junyi Zhang & Vidhya M. Ravi & Kevin Joseph & Roman Sankowski & Jürgen Beck & Catalina Lee-Chang & Oliver Schnell & Dieter Henrik Heiland, 2023. "High-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43201-6
    DOI: 10.1038/s41467-023-43201-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43201-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-43201-6?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. Kevin Lebrigand & Virginie Magnone & Pascal Barbry & Rainer Waldmann, 2020. "High throughput error corrected Nanopore single cell transcriptome sequencing," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    2. Mandeep Singh & Ghamdan Al-Eryani & Shaun Carswell & James M. Ferguson & James Blackburn & Kirston Barton & Daniel Roden & Fabio Luciani & Tri Giang Phan & Simon Junankar & Katherine Jackson & Christo, 2019. "High-throughput targeted long-read single cell sequencing reveals the clonal and transcriptional landscape of lymphocytes," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    3. Lung‐fei Lee & Jihai Yu, 2016. "Identification of Spatial Durbin Panel Models," Journal of Applied Econometrics, John Wiley & Sons, Ltd., vol. 31(1), pages 133-162, January.
    4. Vidhya M. Ravi & Nicolas Neidert & Paulina Will & Kevin Joseph & Julian P. Maier & Jan Kückelhaus & Lea Vollmer & Jonathan M. Goeldner & Simon P. Behringer & Florian Scherer & Melanie Boerries & Marie, 2022. "T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Christoph Kuppe & Mahmoud M. Ibrahim & Jennifer Kranz & Xiaoting Zhang & Susanne Ziegler & Javier Perales-Patón & Jitske Jansen & Katharina C. Reimer & James R. Smith & Ross Dobie & John R. Wilson-Kan, 2021. "Decoding myofibroblast origins in human kidney fibrosis," Nature, Nature, vol. 589(7841), pages 281-286, January.
    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. Jan Kueckelhaus & Simon Frerich & Jasim Kada-Benotmane & Christina Koupourtidou & Jovica Ninkovic & Martin Dichgans & Juergen Beck & Oliver Schnell & Dieter Henrik Heiland, 2024. "Inferring histology-associated gene expression gradients in spatial transcriptomic studies," Nature Communications, Nature, vol. 15(1), pages 1-19, 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. Ashley Byrne & Daniel Le & Kostianna Sereti & Hari Menon & Samir Vaidya & Neha Patel & Jessica Lund & Ana Xavier-Magalhães & Minyi Shi & Yuxin Liang & Timothy Sterne-Weiler & Zora Modrusan & William S, 2024. "Single-cell long-read targeted sequencing reveals transcriptional variation in ovarian cancer," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Marie Bobowski-Gerard & Clémence Boulet & Francesco P. Zummo & Julie Dubois-Chevalier & Céline Gheeraert & Mohamed Bou Saleh & Jean-Marc Strub & Amaury Farce & Maheul Ploton & Loïc Guille & Jimmy Vand, 2022. "Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Raymond Hall Yip Louie & Curtis Cai & Jerome Samir & Mandeep Singh & Ira W. Deveson & James M. Ferguson & Timothy G. Amos & Helen Marie McGuire & Kavitha Gowrishankar & Thiruni Adikari & Robert Balder, 2023. "CAR+ and CAR− T cells share a differentiation trajectory into an NK-like subset after CD19 CAR T cell infusion in patients with B cell malignancies," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Giovanni Millo, 2024. "An Ad Hoc Procedure for Testing Serial Correlation in Spatial Fixed-Effects Panels," Mathematics, MDPI, vol. 12(10), pages 1-18, May.
    5. Livius Penter & Mehdi Borji & Adi Nagler & Haoxiang Lyu & Wesley S. Lu & Nicoletta Cieri & Katie Maurer & Giacomo Oliveira & Aziz M. Al’Khafaji & Kiran V. Garimella & Shuqiang Li & Donna S. Neuberg & , 2024. "Integrative genotyping of cancer and immune phenotypes by long-read sequencing," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Pino, Gabriel, 2022. "Did small or large US banks transmit more risk during the Subprime crisis?," The North American Journal of Economics and Finance, Elsevier, vol. 59(C).
    7. Shi, Wei & Lee, Lung-fei, 2017. "Spatial dynamic panel data models with interactive fixed effects," Journal of Econometrics, Elsevier, vol. 197(2), pages 323-347.
    8. Baltagi, Badi H. & Fingleton, Bernard & Pirotte, Alain, 2019. "A time-space dynamic panel data model with spatial moving average errors," Regional Science and Urban Economics, Elsevier, vol. 76(C), pages 13-31.
    9. Yu Wang & Zhi-Ying Guan & Shao-Wen Shi & Yi-Rong Jiang & Jie Zhang & Yi Yang & Qiong Wu & Jie Wu & Jian-Bo Chen & Wei-Xin Ying & Qin-Qin Xu & Qian-Xi Fan & Hui-Feng Wang & Li Zhou & Ling Wang & Jin Fa, 2024. "Pick-up single-cell proteomic analysis for quantifying up to 3000 proteins in a Mammalian cell," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. Kun Duan & Tapas Mishra & Mamata Parhi & Simon Wolfe, 2019. "How Effective are Policy Interventions in a Spatially-Embedded International Real Estate Market?," The Journal of Real Estate Finance and Economics, Springer, vol. 58(4), pages 596-637, May.
    11. Haojia Wu & Eryn E. Dixon & Qiao Xuanyuan & Juanru Guo & Yasuhiro Yoshimura & Chitnis Debashish & Anezka Niesnerova & Hao Xu & Morgane Rouault & Benjamin D. Humphreys, 2024. "High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    12. Manjón Antolín, M. & Martinez Ibañez, Oscar, 2019. "Growth with heterogenous interdependence," DES - Working Papers. Statistics and Econometrics. WS 29023, Universidad Carlos III de Madrid. Departamento de Estadística.
    13. Baltagi, Badi H. & Pirotte, Alain & Yang, Zhenlin, 2021. "Diagnostic tests for homoskedasticity in spatial cross-sectional or panel models," Journal of Econometrics, Elsevier, vol. 224(2), pages 245-270.
    14. Cynthia Fan Yang, 2021. "Common factors and spatial dependence: an application to US house prices," Econometric Reviews, Taylor & Francis Journals, vol. 40(1), pages 14-50, January.
    15. Li, Liyao & Yang, Zhenlin, 2021. "Spatial dynamic panel data models with correlated random effects," Journal of Econometrics, Elsevier, vol. 221(2), pages 424-454.
    16. Dylan Scott Lykke Harwood & Vilde Pedersen & Nicolai Schou Bager & Ane Yde Schmidt & Tobias Overlund Stannius & Aušrinė Areškevičiūtė & Knud Josefsen & Dorte Schou Nørøxe & David Scheie & Hannah Rosta, 2024. "Glioblastoma cells increase expression of notch signaling and synaptic genes within infiltrated brain tissue," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    17. Anna Gloria Billé & Samantha Leorato, 2017. "Quasi-ML estimation, Marginal Effects and Asymptotics for Spatial Autoregressive Nonlinear Models," BEMPS - Bozen Economics & Management Paper Series BEMPS44, Faculty of Economics and Management at the Free University of Bozen.
    18. Zhiping Zhang & Bongmin Bae & Winston H. Cuddleston & Pedro Miura, 2023. "Coordination of alternative splicing and alternative polyadenylation revealed by targeted long read sequencing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    19. Shirong Cao & Yu Pan & Andrew S. Terker & Juan Pablo Arroyo Ornelas & Yinqiu Wang & Jiaqi Tang & Aolei Niu & Sarah Abu Kar & Mengdi Jiang & Wentian Luo & Xinyu Dong & Xiaofeng Fan & Suwan Wang & Matth, 2023. "Epidermal growth factor receptor activation is essential for kidney fibrosis development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    20. LiangYu Zhao & Sha Han & HengChuan Su & JianYing Li & ErLei Zhi & Peng Li & ChenCheng Yao & RuHui Tian & HuiXing Chen & HuiRong Chen & JiaQiang Luo & ChenKun Shi & ZhiYong Ji & JianLin Hu & Gang Wu & , 2022. "Single-cell transcriptome atlas of the human corpus cavernosum," Nature Communications, Nature, vol. 13(1), pages 1-16, 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:14:y:2023:i:1:d:10.1038_s41467-023-43201-6. 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.