IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45341-9.html
   My bibliography  Save this article

A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution

Author

Listed:
  • Michael T. H. Ng

    (University of Oxford)

  • Rowie Borst

    (University of Oxford)

  • Hamez Gacaferi

    (University of Oxford)

  • Sarah Davidson

    (University of Oxford)

  • Jessica E. Ackerman

    (University of Oxford)

  • Peter A. Johnson

    (University of Oxford)

  • Caio C. Machado

    (University of Oxford
    University of Sao Paulo)

  • Ian Reekie

    (University of Oxford)

  • Moustafa Attar

    (University of Oxford)

  • Dylan Windell

    (University of Oxford)

  • Mariola Kurowska-Stolarska

    (University of Glasgow)

  • Lucy MacDonald

    (University of Glasgow)

  • Stefano Alivernini

    (Fondazione Policlinico Universitario Agostino Gemelli – IRCCS)

  • Micon Garvilles

    (University of Oxford)

  • Kathrin Jansen

    (University of Oxford)

  • Ananya Bhalla

    (University of Oxford)

  • Angela Lee

    (University of Oxford)

  • James Charlesworth

    (University of Oxford)

  • Rajat Chowdhury

    (University of Oxford)

  • Paul Klenerman

    (University of Oxford)

  • Kate Powell

    (University of Oxford)

  • Carl-Philip Hackstein

    (University of Oxford)

  • Dominic Furniss

    (University of Oxford)

  • Jonathan Rees

    (University of Oxford)

  • Derek Gilroy

    (University College London)

  • Mark Coles

    (University of Oxford)

  • Andrew J. Carr

    (University of Oxford)

  • Stephen N. Sansom

    (University of Oxford)

  • Christopher D. Buckley

    (University of Oxford)

  • Stephanie G. Dakin

    (University of Oxford)

Abstract

Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKlowCD48+ macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution. Cross-tissue analysis reveals a shared gene expression cassette between shoulder capsule MERTK+ macrophages and a respective population enriched in synovial tissues of rheumatoid arthritis patients in disease remission, supporting the concept that MERTK+ macrophages mediate resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identify MERTK + LYVE1 + MRC1+ macrophages and DKK3+ and POSTN+ fibroblast populations analogous to those in frozen shoulder, suggesting that the template to resolve fibrosis is established during shoulder development. Crosstalk between MerTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts could facilitate resolution of frozen shoulder, providing a basis for potential therapeutic resolution of persistent fibrotic diseases.

Suggested Citation

  • Michael T. H. Ng & Rowie Borst & Hamez Gacaferi & Sarah Davidson & Jessica E. Ackerman & Peter A. Johnson & Caio C. Machado & Ian Reekie & Moustafa Attar & Dylan Windell & Mariola Kurowska-Stolarska &, 2024. "A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45341-9
    DOI: 10.1038/s41467-024-45341-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45341-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-45341-9?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 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.
    2. Rui Hou & Elena Denisenko & Huan Ting Ong & Jordan A. Ramilowski & Alistair R. R. Forrest, 2020. "Predicting cell-to-cell communication networks using NATMI," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    3. M. Büttner & J. Ostner & C. L. Müller & F. J. Theis & B. Schubert, 2021. "scCODA is a Bayesian model for compositional single-cell data analysis," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    4. Xuran Wang & Jihwan Park & Katalin Susztak & Nancy R. Zhang & Mingyao Li, 2019. "Bulk tissue cell type deconvolution with multi-subject single-cell expression reference," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    5. Harry D Green & Alistair Jones & Jonathan P Evans & Andrew R Wood & Robin N Beaumont & Jessica Tyrrell & Timothy M Frayling & Christopher Smith & Michael N Weedon, 2021. "A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor," PLOS Genetics, Public Library of Science, vol. 17(6), pages 1-13, June.
    6. P. Ramachandran & R. Dobie & J. R. Wilson-Kanamori & E. F. Dora & B. E. P. Henderson & N. T. Luu & J. R. Portman & K. P. Matchett & M. Brice & J. A. Marwick & R. S. Taylor & M. Efremova & R. Vento-Tor, 2019. "Resolving the fibrotic niche of human liver cirrhosis at single-cell level," Nature, Nature, vol. 575(7783), pages 512-518, November.
    Full references (including those not matched with items on IDEAS)

    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. Caitriona M. McEvoy & Julia M. Murphy & Lin Zhang & Sergi Clotet-Freixas & Jessica A. Mathews & James An & Mehran Karimzadeh & Delaram Pouyabahar & Shenghui Su & Olga Zaslaver & Hannes Röst & Rangi Ar, 2022. "Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Bárbara Andrade Barbosa & Saskia D. Asten & Ji Won Oh & Arantza Farina-Sarasqueta & Joanne Verheij & Frederike Dijk & Hanneke W. M. Laarhoven & Bauke Ylstra & Juan J. Garcia Vallejo & Mark A. Wiel & Y, 2021. "Bayesian log-normal deconvolution for enhanced in silico microdissection of bulk gene expression data," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Keyong Sun & Runda Xu & Fuhai Ma & Naixue Yang & Yang Li & Xiaofeng Sun & Peng Jin & Wenzhe Kang & Lemei Jia & Jianping Xiong & Haitao Hu & Yantao Tian & Xun Lan, 2022. "scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Magnus Zethoven & Luciano Martelotto & Andrew Pattison & Blake Bowen & Shiva Balachander & Aidan Flynn & Fernando J. Rossello & Annette Hogg & Julie A. Miller & Zdenek Frysak & Sean Grimmond & Lauren , 2022. "Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    5. Agnieska Brazovskaja & Tomás Gomes & Rene Holtackers & Philipp Wahle & Christiane Körner & Zhisong He & Theresa Schaffer & Julian Connor Eckel & René Hänsel & Malgorzata Santel & Makiko Seimiya & Timm, 2024. "Cell atlas of the regenerating human liver after portal vein embolization," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Yi Huang & Anyongqi Wang & Wenjiang Zhou & Baoguo Li & Linshan Zhang & Agata M. Rudolf & Zengguang Jin & Catherine Hambly & Guanlin Wang & John R. Speakman, 2024. "Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Meiling Zheng & Zhi Hu & Xiaole Mei & Lianlian Ouyang & Yang Song & Wenhui Zhou & Yi Kong & Ruifang Wu & Shijia Rao & Hai Long & Wei Shi & Hui Jing & Shuang Lu & Haijing Wu & Sujie Jia & Qianjin Lu & , 2022. "Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Matthew C. Hill & Bridget Simonson & Carolina Roselli & Ling Xiao & Caroline N. Herndon & Mark Chaffin & Helene Mantineo & Ondine Atwa & Harshit Bhasin & Yasmine Guedira & Kenneth C. Bedi & Kenneth B., 2024. "Large-scale single-nuclei profiling identifies role for ATRNL1 in atrial fibrillation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. Chang Su & Zichun Xu & Xinning Shan & Biao Cai & Hongyu Zhao & Jingfei Zhang, 2023. "Cell-type-specific co-expression inference from single cell RNA-sequencing data," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    10. Zhenlin Yang & He Tian & Xiaowei Chen & Bozhao Li & Guangyu Bai & Qingyuan Cai & Jiachen Xu & Wei Guo & Shuaibo Wang & Yue Peng & Qing Liang & Liyan Xue & Shugeng Gao, 2024. "Single-cell sequencing reveals immune features of treatment response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    11. Daniel Dimitrov & Dénes Türei & Martin Garrido-Rodriguez & Paul L. Burmedi & James S. Nagai & Charlotte Boys & Ricardo O. Ramirez Flores & Hyojin Kim & Bence Szalai & Ivan G. Costa & Alberto Valdeoliv, 2022. "Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    12. Sophie A. Riesmeijer & Zoha Kamali & Michael Ng & Dmitriy Drichel & Bram Piersma & Kerstin Becker & Thomas B. Layton & Jagdeep Nanchahal & Michael Nothnagel & Ahmad Vaez & Hans Christian Hennies & Pau, 2024. "A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren’s disease," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    13. Xiao Zhou & Zhen Cheng & Mingyu Dong & Qi Liu & Weiyang Yang & Min Liu & Junzhang Tian & Weibin Cheng, 2022. "Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    14. Huachun Cui & Sami Banerjee & Na Xie & Musaddique Hussain & Ashish Jaiswal & Hongli Liu & Tejaswini Kulkarni & Veena B. Antony & Rui-Ming Liu & Marco Colonna & Gang Liu, 2025. "TREM2 promotes lung fibrosis via controlling alveolar macrophage survival and pro-fibrotic activity," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    15. David R. Ghasemi & Konstantin Okonechnikov & Anne Rademacher & Stephan Tirier & Kendra K. Maass & Hanna Schumacher & Piyush Joshi & Maxwell P. Gold & Julia Sundheimer & Britta Statz & Ahmet S. Rifaiog, 2024. "Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    16. Adriana A. de Jesus & Guibin Chen & Dan Yang & Tomas Brdicka & Natasha M. Ruth & David Bennin & Dita Cebecauerova & Hana Malcova & Helen Freeman & Neil Martin & Karel Svojgr & Murray H. Passo & Farzan, 2023. "Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    17. Zhenzhen Xun & Xinyu Ding & Yao Zhang & Benyan Zhang & Shujing Lai & Duowu Zou & Junke Zheng & Guoqiang Chen & Bing Su & Leng Han & Youqiong Ye, 2023. "Reconstruction of the tumor spatial microenvironment along the malignant-boundary-nonmalignant axis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Jessy A. Slota & Lise Lamoureux & Kathy L. Frost & Babu V. Sajesh & Stephanie A. Booth, 2024. "Single-cell transcriptomics unveils molecular signatures of neuronal vulnerability in a mouse model of prion disease that overlap with Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    19. Alessandra Nerviani & Marie-Astrid Boutet & Giulia Maria Ghirardi & Katriona Goldmann & Elisabetta Sciacca & Felice Rivellese & Elena Pontarini & Edoardo Prediletto & Federico Abatecola & Mattia Calis, 2024. "Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    20. Ivan V. Kuzmin & Ruben Soto Acosta & Layne Pruitt & Perry T. Wasdin & Kritika Kedarinath & Keziah R. Hernandez & Kristyn A. Gonzales & Kharighan Hill & Nicole G. Weidner & Chad Mire & Taylor B. Engdah, 2024. "Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine," Nature Communications, Nature, vol. 15(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:15:y:2024:i:1:d:10.1038_s41467-024-45341-9. 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.