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The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis

Author

Listed:
  • Kathryn Weinand

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Harvard Medical School)

  • Saori Sakaue

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Harvard Medical School)

  • Aparna Nathan

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Harvard Medical School)

  • Anna Helena Jonsson

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Fan Zhang

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Harvard Medical School)

  • Gerald F. M. Watts

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Majd Al Suqri

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Zhu Zhu

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Deepak A. Rao

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Jennifer H. Anolik

    (University of Rochester Medical Center)

  • Michael B. Brenner

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Laura T. Donlin

    (Hospital for Special Surgery
    Weill Cornell Medicine)

  • Kevin Wei

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Soumya Raychaudhuri

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Harvard Medical School)

Abstract

Synovial tissue inflammation is a hallmark of rheumatoid arthritis (RA). Recent work has identified prominent pathogenic cell states in inflamed RA synovial tissue, such as T peripheral helper cells; however, the epigenetic regulation of these states has yet to be defined. Here, we examine genome-wide open chromatin at single-cell resolution in 30 synovial tissue samples, including 12 samples with transcriptional data in multimodal experiments. We identify 24 chromatin classes and predict their associated transcription factors, including a CD8 + GZMK+ class associated with EOMES and a lining fibroblast class associated with AP-1. By integrating with an RA tissue transcriptional atlas, we propose that these chromatin classes represent ‘superstates’ corresponding to multiple transcriptional cell states. Finally, we demonstrate the utility of this RA tissue chromatin atlas through the associations between disease phenotypes and chromatin class abundance, as well as the nomination of classes mediating the effects of putatively causal RA genetic variants.

Suggested Citation

  • Kathryn Weinand & Saori Sakaue & Aparna Nathan & Anna Helena Jonsson & Fan Zhang & Gerald F. M. Watts & Majd Al Suqri & Zhu Zhu & Deepak A. Rao & Jennifer H. Anolik & Michael B. Brenner & Laura T. Don, 2024. "The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48620-7
    DOI: 10.1038/s41467-024-48620-7
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    1. Fumitaka Mizoguchi & Kamil Slowikowski & Kevin Wei & Jennifer L. Marshall & Deepak A. Rao & Sook Kyung Chang & Hung N. Nguyen & Erika H. Noss & Jason D. Turner & Brandon E. Earp & Philip E. Blazar & J, 2018. "Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    2. Justin B. Moroney & Anusha Vasudev & Alexander Pertsemlidis & Hong Zan & Paolo Casali, 2020. "Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    3. Bates, Douglas & Mächler, Martin & Bolker, Ben & Walker, Steve, 2015. "Fitting Linear Mixed-Effects Models Using lme4," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 67(i01).
    4. Michael Lawrence & Wolfgang Huber & Hervé Pagès & Patrick Aboyoun & Marc Carlson & Robert Gentleman & Martin T Morgan & Vincent J Carey, 2013. "Software for Computing and Annotating Genomic Ranges," PLOS Computational Biology, Public Library of Science, vol. 9(8), pages 1-10, August.
    5. Matthew B. Buechler & Rachana N. Pradhan & Akshay T. Krishnamurty & Christian Cox & Aslihan Karabacak Calviello & Amber W. Wang & Yeqing Angela Yang & Lucinda Tam & Roger Caothien & Merone Roose-Girma, 2021. "Cross-tissue organization of the fibroblast lineage," Nature, Nature, vol. 593(7860), pages 575-579, May.
    6. Kenji Kamimoto & Blerta Stringa & Christy M. Hoffmann & Kunal Jindal & Lilianna Solnica-Krezel & Samantha A. Morris, 2023. "Dissecting cell identity via network inference and in silico gene perturbation," Nature, Nature, vol. 614(7949), pages 742-751, February.
    7. Deepak A. Rao & Michael F. Gurish & Jennifer L. Marshall & Kamil Slowikowski & Chamith Y. Fonseka & Yanyan Liu & Laura T. Donlin & Lauren A. Henderson & Kevin Wei & Fumitaka Mizoguchi & Nikola C. Tesl, 2017. "Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis," Nature, Nature, vol. 542(7639), pages 110-114, February.
    8. Monica Corada & Fabrizio Orsenigo & Marco Francesco Morini & Mara Elena Pitulescu & Ganesh Bhat & Daniel Nyqvist & Ferruccio Breviario & Valentina Conti & Anais Briot & M. Luisa Iruela-Arispe & Ralf H, 2013. "Sox17 is indispensable for acquisition and maintenance of arterial identity," Nature Communications, Nature, vol. 4(1), pages 1-14, December.
    9. Piotr Bielecki & Samantha J. Riesenfeld & Jan-Christian Hütter & Elena Torlai Triglia & Monika S. Kowalczyk & Roberto R. Ricardo-Gonzalez & Mi Lian & Maria C. Amezcua Vesely & Lina Kroehling & Hao Xu , 2021. "Skin-resident innate lymphoid cells converge on a pathogenic effector state," Nature, Nature, vol. 592(7852), pages 128-132, April.
    10. Aparna Nathan & Samira Asgari & Kazuyoshi Ishigaki & Cristian Valencia & Tiffany Amariuta & Yang Luo & Jessica I. Beynor & Yuriy Baglaenko & Sara Suliman & Alkes L. Price & Leonid Lecca & Megan B. Mur, 2022. "Single-cell eQTL models reveal dynamic T cell state dependence of disease loci," Nature, Nature, vol. 606(7912), pages 120-128, June.
    11. Joyce B. Kang & Aparna Nathan & Kathryn Weinand & Fan Zhang & Nghia Millard & Laurie Rumker & D. Branch Moody & Ilya Korsunsky & Soumya Raychaudhuri, 2021. "Efficient and precise single-cell reference atlas mapping with Symphony," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    12. Amartya Sanyal & Bryan R. Lajoie & Gaurav Jain & Job Dekker, 2012. "The long-range interaction landscape of gene promoters," Nature, Nature, vol. 489(7414), pages 109-113, September.
    13. Kevin Wei & Ilya Korsunsky & Jennifer L. Marshall & Anqi Gao & Gerald F. M. Watts & Triin Major & Adam P. Croft & Jordan Watts & Philip E. Blazar & Jeffrey K. Lange & Thomas S. Thornhill & Andrew File, 2020. "Notch signalling drives synovial fibroblast identity and arthritis pathology," Nature, Nature, vol. 582(7811), pages 259-264, June.
    14. Simon N. Willis & Julie Tellier & Yang Liao & Stephanie Trezise & Amanda Light & Kristy O’Donnell & Lee Ann Garrett-Sinha & Wei Shi & David M. Tarlinton & Stephen L. Nutt, 2017. "Environmental sensing by mature B cells is controlled by the transcription factors PU.1 and SpiB," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
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