IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50564-x.html
   My bibliography  Save this article

Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys

Author

Listed:
  • Xiaoyu Xue

    (Chinese Academy of Sciences)

  • Xianming Wu

    (Chinese Academy of Sciences)

  • Yongheng Fan

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shuyu Han

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Haipeng Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yuting Sun

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yanyun Yin

    (Chinese Academy of Sciences)

  • Man Yin

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Bing Chen

    (Chinese Academy of Sciences)

  • Zheng Sun

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shuaijing Zhao

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Qi Zhang

    (Chinese Academy of Sciences)

  • Weiyuan Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jiaojiao Zhang

    (Chinese Academy of Sciences)

  • Jiayin Li

    (Chinese Academy of Sciences)

  • Ya Shi

    (Chinese Academy of Sciences)

  • Zhifeng Xiao

    (Chinese Academy of Sciences)

  • Jianwu Dai

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Yannan Zhao

    (Chinese Academy of Sciences)

Abstract

Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cholesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI.

Suggested Citation

  • Xiaoyu Xue & Xianming Wu & Yongheng Fan & Shuyu Han & Haipeng Zhang & Yuting Sun & Yanyun Yin & Man Yin & Bing Chen & Zheng Sun & Shuaijing Zhao & Qi Zhang & Weiyuan Liu & Jiaojiao Zhang & Jiayin Li &, 2024. "Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50564-x
    DOI: 10.1038/s41467-024-50564-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50564-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-50564-x?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. Michael Vanlandewijck & Liqun He & Maarja Andaloussi Mäe & Johanna Andrae & Koji Ando & Francesca Gaudio & Khayrun Nahar & Thibaud Lebouvier & Bàrbara Laviña & Leonor Gouveia & Ying Sun & Elisabeth Ra, 2018. "Author Correction: A molecular atlas of cell types and zonation in the brain vasculature," Nature, Nature, vol. 560(7716), pages 3-3, August.
    2. Roser Vento-Tormo & Mirjana Efremova & Rachel A. Botting & Margherita Y. Turco & Miquel Vento-Tormo & Kerstin B. Meyer & Jong-Eun Park & Emily Stephenson & Krzysztof Polański & Angela Goncalves & Lucy, 2018. "Single-cell reconstruction of the early maternal–fetal interface in humans," Nature, Nature, vol. 563(7731), pages 347-353, November.
    3. David O. Dias & Jannis Kalkitsas & Yildiz Kelahmetoglu & Cynthia P. Estrada & Jemal Tatarishvili & Daniel Holl & Linda Jansson & Shervin Banitalebi & Mahmood Amiry-Moghaddam & Aurélie Ernst & Hagen B., 2021. "Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    4. Yi Li & Xuelian He & Riki Kawaguchi & Yu Zhang & Qing Wang & Aboozar Monavarfeshani & Zhiyun Yang & Bo Chen & Zhongju Shi & Huyan Meng & Songlin Zhou & Junjie Zhu & Anne Jacobi & Vivek Swarup & Philli, 2020. "Microglia-organized scar-free spinal cord repair in neonatal mice," Nature, Nature, vol. 587(7835), pages 613-618, November.
    5. Michael Vanlandewijck & Liqun He & Maarja Andaloussi Mäe & Johanna Andrae & Koji Ando & Francesca Del Gaudio & Khayrun Nahar & Thibaud Lebouvier & Bàrbara Laviña & Leonor Gouveia & Ying Sun & Elisabet, 2018. "A molecular atlas of cell types and zonation in the brain vasculature," Nature, Nature, vol. 554(7693), pages 475-480, February.
    6. Michael V. Sofroniew, 2018. "Dissecting spinal cord regeneration," Nature, Nature, vol. 557(7705), pages 343-350, May.
    7. Daniel Wehner & Themistoklis M. Tsarouchas & Andria Michael & Christa Haase & Gilbert Weidinger & Michell M. Reimer & Thomas Becker & Catherina G. Becker, 2017. "Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    8. Andrew C. Yang & Ryan T. Vest & Fabian Kern & Davis P. Lee & Maayan Agam & Christina A. Maat & Patricia M. Losada & Michelle B. Chen & Nicholas Schaum & Nathalie Khoury & Angus Toland & Kruti Calcutta, 2022. "A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk," Nature, Nature, vol. 603(7903), pages 885-892, March.
    9. Yongheng Fan & Xianming Wu & Sufang Han & Qi Zhang & Zheng Sun & Bing Chen & Xiaoyu Xue & Haipeng Zhang & Zhenni Chen & Man Yin & Zhifeng Xiao & Yannan Zhao & Jianwu Dai, 2023. "Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    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. Lin Wei Tung & Elena Groppa & Hesham Soliman & Bruce Lin & Chihkai Chang & Chun Wai Cheung & Morten Ritso & David Guo & Lucas Rempel & Sarthak Sinha & Christine Eisner & Julyanne Brassard & Kelly McNa, 2023. "Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Stergios Tsartsalis & Hannah Sleven & Nurun Fancy & Frank Wessely & Amy M. Smith & Nanet Willumsen & To Ka Dorcas Cheung & Michal J. Rokicki & Vicky Chau & Eseoghene Ifie & Combiz Khozoie & Olaf Ansor, 2024. "A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Airi Jo-Watanabe & Toshiki Inaba & Takahiro Osada & Ryota Hashimoto & Tomohiro Nishizawa & Toshiaki Okuno & Sayoko Ihara & Kazushige Touhara & Nobutaka Hattori & Masatsugu Oh-Hora & Osamu Nureki & Tak, 2024. "Bicarbonate signalling via G protein-coupled receptor regulates ischaemia-reperfusion injury," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Xinrui Zhou & Wan Yi Seow & Norbert Ha & Teh How Cheng & Lingfan Jiang & Jeeranan Boonruangkan & Jolene Jie Lin Goh & Shyam Prabhakar & Nigel Chou & Kok Hao Chen, 2024. "Highly sensitive spatial transcriptomics using FISHnCHIPs of multiple co-expressed genes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Kevin Boyé & Luiz Henrique Geraldo & Jessica Furtado & Laurence Pibouin-Fragner & Mathilde Poulet & Doyeun Kim & Bryce Nelson & Yunling Xu & Laurent Jacob & Nawal Maissa & Dritan Agalliu & Lena Claess, 2022. "Endothelial Unc5B controls blood-brain barrier integrity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Amy J. Gleichman & Riki Kawaguchi & Michael V. Sofroniew & S. Thomas Carmichael, 2023. "A toolbox of astrocyte-specific, serotype-independent adeno-associated viral vectors using microRNA targeting sequences," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Xiang He & Daiqin Xiong & Lei Zhao & Jialong Fu & Lingfei Luo, 2024. "Meningeal lymphatic supporting cells govern the formation and maintenance of zebrafish mural lymphatic endothelial cells," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Martin Uhrbom & Lars Muhl & Guillem Genové & Jianping Liu & Henrik Palmgren & Ida Alexandersson & Fredrik Karlsson & Alex-Xianghua Zhou & Sandra Lunnerdal & Sonja Gustafsson & Byambajav Buyandelger & , 2024. "Adipose stem cells are sexually dimorphic cells with dual roles as preadipocytes and resident fibroblasts," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    9. Kaya J. E. Matson & Daniel E. Russ & Claudia Kathe & Isabelle Hua & Dragan Maric & Yi Ding & Jonathan Krynitsky & Randall Pursley & Anupama Sathyamurthy & Jordan W. Squair & Boaz P. Levi & Gregoire Co, 2022. "Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. Shujuan Zhao & Kedous Y. Mekbib & Martijn A. Ent & Garrett Allington & Andrew Prendergast & Jocelyn E. Chau & Hannah Smith & John Shohfi & Jack Ocken & Daniel Duran & Charuta G. Furey & Le Thi Hao & P, 2023. "Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    11. Chris Greene & Nicole Hanley & Cristina R. Reschke & Avril Reddy & Maarja A. Mäe & Ruairi Connolly & Claire Behan & Eoin O’Keeffe & Isobel Bolger & Natalie Hudson & Conor Delaney & Michael A. Farrell , 2022. "Microvascular stabilization via blood-brain barrier regulation prevents seizure activity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    12. Vishnu Muraleedharan Saraswathy & Lili Zhou & Mayssa H. Mokalled, 2024. "Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    13. Xiaomeng Wan & Jiashun Xiao & Sindy Sing Ting Tam & Mingxuan Cai & Ryohichi Sugimura & Yang Wang & Xiang Wan & Zhixiang Lin & Angela Ruohao Wu & Can Yang, 2023. "Integrating spatial and single-cell transcriptomics data using deep generative models with SpatialScope," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    14. Laetitia Préau & Anna Lischke & Melanie Merkel & Neslihan Oegel & Maria Weissenbruch & Andria Michael & Hongryeol Park & Dietmar Gradl & Christian Kupatt & Ferdinand Noble, 2024. "Parenchymal cues define Vegfa-driven venous angiogenesis by activating a sprouting competent venous endothelial subtype," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    15. Amira Sayed Hanafy & Pia Steinlein & Julika Pitsch & Mariella Hurtado Silva & Natascha Vana & Albert J. Becker & Mark Evan Graham & Susanne Schoch & Alf Lamprecht & Dirk Dietrich, 2023. "Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    16. Nicholas W. Chavkin & Gael Genet & Mathilde Poulet & Erin D. Jeffery & Corina Marziano & Nafiisha Genet & Hema Vasavada & Elizabeth A. Nelson & Bipul R. Acharya & Anupreet Kour & Jordon Aragon & Steph, 2022. "Endothelial cell cycle state determines propensity for arterial-venous fate," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    17. Martin Arostegui & R. Wilder Scott & Kerstin Böse & T. Michael Underhill, 2022. "Cellular taxonomy of Hic1+ mesenchymal progenitor derivatives in the limb: from embryo to adult," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    18. Moises Freitas-Andrade & Cesar H. Comin & Peter Dyken & Julie Ouellette & Joanna Raman-Nair & Nicole Blakeley & Qing Yan Liu & Sonia Leclerc & Youlian Pan & Ziying Liu & Micaël Carrier & Karan Thakur , 2023. "Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    19. Yutong Guo & Hohyun Lee & Chulyong Kim & Christian Park & Akane Yamamichi & Pavlina Chuntova & Marco Gallus & Miguel O. Bernabeu & Hideho Okada & Hanjoong Jo & Costas Arvanitis, 2024. "Ultrasound frequency-controlled microbubble dynamics in brain vessels regulate the enrichment of inflammatory pathways in the blood-brain barrier," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    20. Jeremiah Bernier-Latmani & Cristina Mauri & Rachel Marcone & François Renevey & Stephan Durot & Liqun He & Michael Vanlandewijck & Catherine Maclachlan & Suzel Davanture & Nicola Zamboni & Graham W. K, 2022. "ADAMTS18+ villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels," Nature Communications, Nature, vol. 13(1), pages 1-17, 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_s41467-024-50564-x. 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.