IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48663-w.html
   My bibliography  Save this article

Retrotransposons in Werner syndrome-derived macrophages trigger type I interferon-dependent inflammation in an atherosclerosis model

Author

Listed:
  • Sudip Kumar Paul

    (Chiba University)

  • Motohiko Oshima

    (The University of Tokyo)

  • Ashwini Patil

    (Combinatics Inc.)

  • Masamitsu Sone

    (Chiba University
    Hokkaido University)

  • Hisaya Kato

    (Chiba University)

  • Yoshiro Maezawa

    (Chiba University)

  • Hiyori Kaneko

    (Chiba University)

  • Masaki Fukuyo

    (Chiba University)

  • Bahityar Rahmutulla

    (Chiba University)

  • Yasuo Ouchi

    (Chiba University
    Salk Institute for Biological Studies)

  • Kyoko Tsujimura

    (Chiba University)

  • Mahito Nakanishi

    (Inc.)

  • Atsushi Kaneda

    (Chiba University)

  • Atsushi Iwama

    (The University of Tokyo)

  • Koutaro Yokote

    (Chiba University)

  • Koji Eto

    (Chiba University
    Kyoto University)

  • Naoya Takayama

    (Chiba University)

Abstract

The underlying mechanisms of atherosclerosis, the second leading cause of death among Werner syndrome (WS) patients, are not fully understood. Here, we establish an in vitro co-culture system using macrophages (iMφs), vascular endothelial cells (iVECs), and vascular smooth muscle cells (iVSMCs) derived from induced pluripotent stem cells. In co-culture, WS-iMφs induces endothelial dysfunction in WS-iVECs and characteristics of the synthetic phenotype in WS-iVSMCs. Transcriptomics and open chromatin analysis reveal accelerated activation of type I interferon signaling and reduced chromatin accessibility of several transcriptional binding sites required for cellular homeostasis in WS-iMφs. Furthermore, the H3K9me3 levels show an inverse correlation with retrotransposable elements, and retrotransposable element-derived double-stranded RNA activates the DExH-box helicase 58 (DHX58)-dependent cytoplasmic RNA sensing pathway in WS-iMφs. Conversely, silencing type I interferon signaling in WS-iMφs rescues cell proliferation and suppresses cellular senescence and inflammation. These findings suggest that Mφ-specific inhibition of type I interferon signaling could be targeted to treat atherosclerosis in WS patients.

Suggested Citation

  • Sudip Kumar Paul & Motohiko Oshima & Ashwini Patil & Masamitsu Sone & Hisaya Kato & Yoshiro Maezawa & Hiyori Kaneko & Masaki Fukuyo & Bahityar Rahmutulla & Yasuo Ouchi & Kyoko Tsujimura & Mahito Nakan, 2024. "Retrotransposons in Werner syndrome-derived macrophages trigger type I interferon-dependent inflammation in an atherosclerosis model," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48663-w
    DOI: 10.1038/s41467-024-48663-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48663-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-48663-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. Vera Gorbunova & Andrei Seluanov & Paolo Mita & Wilson McKerrow & David Fenyö & Jef D. Boeke & Sara B. Linker & Fred H. Gage & Jill A. Kreiling & Anna P. Petrashen & Trenton A. Woodham & Jackson R. Ta, 2021. "The role of retrotransposable elements in ageing and age-associated diseases," Nature, Nature, vol. 596(7870), pages 43-53, August.
    2. Jie Wang & Cristina Zibetti & Peng Shang & Srinivasa R. Sripathi & Pingwu Zhang & Marisol Cano & Thanh Hoang & Shuli Xia & Hongkai Ji & Shannath L. Merbs & Donald J. Zack & James T. Handa & Debasish S, 2018. "ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    3. Naoki Itokawa & Motohiko Oshima & Shuhei Koide & Naoya Takayama & Wakako Kuribayashi & Yaeko Nakajima-Takagi & Kazumasa Aoyama & Satoshi Yamazaki & Kiyoshi Yamaguchi & Yoichi Furukawa & Koji Eto & Ats, 2022. "Epigenetic traits inscribed in chromatin accessibility in aged hematopoietic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Marco Cecco & Takahiro Ito & Anna P. Petrashen & Amy E. Elias & Nicholas J. Skvir & Steven W. Criscione & Alberto Caligiana & Greta Brocculi & Emily M. Adney & Jef D. Boeke & Oanh Le & Christian Beaus, 2019. "L1 drives IFN in senescent cells and promotes age-associated inflammation," Nature, Nature, vol. 566(7742), pages 73-78, February.
    5. Marco Cecco & Takahiro Ito & Anna P. Petrashen & Amy E. Elias & Nicholas J. Skvir & Steven W. Criscione & Alberto Caligiana & Greta Brocculi & Emily M. Adney & Jef D. Boeke & Oanh Le & Christian Beaus, 2019. "Author Correction: L1 drives IFN in senescent cells and promotes age-associated inflammation," Nature, Nature, vol. 572(7767), pages 5-5, August.
    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. Yung-Heng Chang & Josh Dubnau, 2023. "Endogenous retroviruses and TDP-43 proteinopathy form a sustaining feedback driving intercellular spread of Drosophila neurodegeneration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Yang Yu & Xin Wang & Jordan Fox & Ruofan Yu & Pilendra Thakre & Brenna McCauley & Nicolas Nikoloutsos & Yang Yu & Qian Li & P. J. Hastings & Weiwei Dang & Kaifu Chen & Grzegorz Ira, 2024. "Yeast EndoG prevents genome instability by degrading extranuclear DNA species," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Ioana Olan & Masami Ando-Kuri & Aled J. Parry & Tetsuya Handa & Stefan Schoenfelder & Peter Fraser & Yasuyuki Ohkawa & Hiroshi Kimura & Masako Narita & Masashi Narita, 2024. "HMGA1 orchestrates chromatin compartmentalization and sequesters genes into 3D networks coordinating senescence heterogeneity," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Alexandra M. D’Ordine & Gerwald Jogl & John M. Sedivy, 2024. "Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Zhengyi Zhen & Yu Chen & Haiyan Wang & Huanyin Tang & Haiping Zhang & Haipeng Liu & Ying Jiang & Zhiyong Mao, 2023. "Nuclear cGAS restricts L1 retrotransposition by promoting TRIM41-mediated ORF2p ubiquitination and degradation," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Bert I. Crawford & Mary Jo Talley & Joshua Russman & James Riddle & Sabrina Torres & Troy Williams & Michelle S. Longworth, 2024. "Condensin-mediated restriction of retrotransposable elements facilitates brain development in Drosophila melanogaster," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    7. Vanessa López-Polo & Mate Maus & Emmanouil Zacharioudakis & Miguel Lafarga & Camille Stephan-Otto Attolini & Francisco D. M. Marques & Marta Kovatcheva & Evripidis Gavathiotis & Manuel Serrano, 2024. "Release of mitochondrial dsRNA into the cytosol is a key driver of the inflammatory phenotype of senescent cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Steven Andrew Baker & Shirley Kwok & Gerald J Berry & Thomas J Montine, 2021. "Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation," PLOS ONE, Public Library of Science, vol. 16(2), pages 1-17, February.
    9. Chunwei Zheng & Bin Liu & Xiaolong Dong & Nicholas Gaston & Erik J. Sontheimer & Wen Xue, 2023. "Template-jumping prime editing enables large insertion and exon rewriting in vivo," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    10. Tsu-Yi Su & Julia Hauenstein & Ece Somuncular & Özge Dumral & Elory Leonard & Charlotte Gustafsson & Efthymios Tzortzis & Aurora Forlani & Anne-Sofie Johansson & Hong Qian & Robert Månsson & Sidinh Lu, 2024. "Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    11. Gangming Zhang & Chunwei Zheng & Yue-he Ding & Craig Mello, 2024. "Casein kinase II promotes piRNA production through direct phosphorylation of USTC component TOFU-4," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    12. Hongna Zuo & Aiwei Wu & Mingwei Wang & Liquan Hong & Hu Wang, 2024. "tRNA m1A modification regulate HSC maintenance and self-renewal via mTORC1 signaling," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    13. Sayan Ghosh & Ruchi Sharma & Sridhar Bammidi & Victoria Koontz & Mihir Nemani & Meysam Yazdankhah & Katarzyna M. Kedziora & Donna Beer Stolz & Callen T. Wallace & Cheng Yu-Wei & Jonathan Franks & Devi, 2024. "The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in non-neovascular AMD," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    14. Ádám Sturm & Éva Saskői & Bernadette Hotzi & Anna Tarnóci & János Barna & Ferenc Bodnár & Himani Sharma & Tibor Kovács & Eszter Ari & Nóra Weinhardt & Csaba Kerepesi & András Perczel & Zoltán Ivics & , 2023. "Downregulation of transposable elements extends lifespan in Caenorhabditis elegans," 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:15:y:2024:i:1:d:10.1038_s41467-024-48663-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.