IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37589-4.html
   My bibliography  Save this article

Embryonic keratin19+ progenitors generate multiple functionally distinct progeny to maintain epithelial diversity in the adult thymus medulla

Author

Listed:
  • Beth Lucas

    (University of Birmingham)

  • Andrea J. White

    (University of Birmingham)

  • Fabian Klein

    (University of Oxford)

  • Clara Veiga-Villauriz

    (University of Oxford)

  • Adam Handel

    (University of Oxford
    University of Oxford)

  • Andrea Bacon

    (University of Birmingham)

  • Emilie J. Cosway

    (University of Birmingham)

  • Kieran D. James

    (University of Birmingham)

  • Sonia M. Parnell

    (University of Birmingham)

  • Izumi Ohigashi

    (Tokushima University)

  • Yousuke Takahama

    (Experimental Immunology Branch, NCI/NIH)

  • William E. Jenkinson

    (University of Birmingham)

  • Georg A. Hollander

    (University of Oxford
    University of Basel and University Children’s Hospital Basel
    ETH Zurich)

  • Wei-Yu Lu

    (University of Edinburgh)

  • Graham Anderson

    (University of Birmingham)

Abstract

The thymus medulla is a key site for immunoregulation and tolerance, and its functional specialisation is achieved through the complexity of medullary thymic epithelial cells (mTEC). While the importance of the medulla for thymus function is clear, the production and maintenance of mTEC diversity remains poorly understood. Here, using ontogenetic and inducible fate-mapping approaches, we identify mTEC-restricted progenitors as a cytokeratin19+ (K19+) TEC subset that emerges in the embryonic thymus. Importantly, labelling of a single cohort of K19+ TEC during embryogenesis sustains the production of multiple mTEC subsets into adulthood, including CCL21+ mTEClo, Aire+ mTEChi and thymic tuft cells. We show K19+ progenitors arise prior to the acquisition of multiple mTEC-defining features including RANK and CCL21 and are generated independently of the key mTEC regulator, Relb. In conclusion, we identify and define a multipotent mTEC progenitor that emerges during embryogenesis to support mTEC diversity into adult life.

Suggested Citation

  • Beth Lucas & Andrea J. White & Fabian Klein & Clara Veiga-Villauriz & Adam Handel & Andrea Bacon & Emilie J. Cosway & Kieran D. James & Sonia M. Parnell & Izumi Ohigashi & Yousuke Takahama & William E, 2023. "Embryonic keratin19+ progenitors generate multiple functionally distinct progeny to maintain epithelial diversity in the adult thymus medulla," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37589-4
    DOI: 10.1038/s41467-023-37589-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37589-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-37589-4?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. Beth Lucas & Andrea J. White & Emilie J. Cosway & Sonia M. Parnell & Kieran D. James & Nick D. Jones & Izumi Ohigashi & Yousuke Takahama & William E. Jenkinson & Graham Anderson, 2020. "Diversity in medullary thymic epithelial cells controls the activity and availability of iNKT cells," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Alexander Raven & Wei-Yu Lu & Tak Yung Man & Sofia Ferreira-Gonzalez & Eoghan O’Duibhir & Benjamin J. Dwyer & John P. Thomson & Richard R. Meehan & Roman Bogorad & Victor Koteliansky & Yuri Kotelevtse, 2017. "Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration," Nature, Nature, vol. 547(7663), pages 350-354, July.
    3. Jennifer E. Cowan & Justin Malin & Yongge Zhao & Mina O. Seedhom & Christelle Harly & Izumi Ohigashi & Michael Kelly & Yousuke Takahama & Jonathan W. Yewdell & Maggie Cam & Avinash Bhandoola, 2019. "Myc controls a distinct transcriptional program in fetal thymic epithelial cells that determines thymus growth," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    4. Corey N. Miller & Irina Proekt & Jakob Moltke & Kristen L. Wells & Aparna R. Rajpurkar & Haiguang Wang & Kristin Rattay & Imran S. Khan & Todd C. Metzger & Joshua L. Pollack & Adam C. Fries & Wint W. , 2018. "Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development," Nature, Nature, vol. 559(7715), pages 627-631, July.
    5. Anja Nusser & Sagar & Jeremy B. Swann & Brigitte Krauth & Dagmar Diekhoff & Lesly Calderon & Christiane Happe & Dominic Grün & Thomas Boehm, 2022. "Developmental dynamics of two bipotent thymic epithelial progenitor types," Nature, Nature, vol. 606(7912), pages 165-171, June.
    6. Margaret E. Magaletta & Macrina Lobo & Eric M. Kernfeld & Hananeh Aliee & Jack D. Huey & Teagan J. Parsons & Fabian J. Theis & René Maehr, 2022. "Integration of single-cell transcriptomes and chromatin landscapes reveals regulatory programs driving pharyngeal organ development," Nature Communications, Nature, vol. 13(1), pages 1-16, 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. Fabian Klein & Clara Veiga-Villauriz & Anastasiya Börsch & Stefano Maio & Sam Palmer & Fatima Dhalla & Adam E. Handel & Saulius Zuklys & Irene Calvo-Asensio & Lucas Musette & Mary E. Deadman & Andrea , 2023. "Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Zhongwei Xin & Mingjie Lin & Zhixing Hao & Di Chen & Yongyuan Chen & Xiaoke Chen & Xia Xu & Jinfan Li & Dang Wu & Ying Chai & Pin Wu, 2022. "The immune landscape of human thymic epithelial tumors," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Xue Zhong & Nagesh Peddada & Jianhui Wang & James J. Moresco & Xiaowei Zhan & John M. Shelton & Jeffrey A. SoRelle & Katie Keller & Danielle Renee Lazaro & Eva Marie Y. Moresco & Jin Huk Choi & Bruce , 2023. "OVOL2 sustains postnatal thymic epithelial cell identity," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    4. Inmaculada Ruz-Maldonado & John T. Gonzalez & Hanming Zhang & Jonathan Sun & Alicia Bort & Inamul Kabir & Richard G. Kibbey & Yajaira Suárez & Daniel M. Greif & Carlos Fernández-Hernando, 2024. "Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    5. Ryan N. O’Keefe & Annalisa L. E. Carli & David Baloyan & David Chisanga & Wei Shi & Shoukat Afshar-Sterle & Moritz F. Eissmann & Ashleigh R. Poh & Bhupinder Pal & Cyril Seillet & Richard M. Locksley &, 2023. "A tuft cell - ILC2 signaling circuit provides therapeutic targets to inhibit gastric metaplasia and tumor development," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Qiang Yu & Igor Gamayun & Philipp Wartenberg & Qian Zhang & Sen Qiao & Soumya Kusumakshi & Sarah Candlish & Viktoria Götz & Shuping Wen & Debajyoti Das & Amanda Wyatt & Vanessa Wahl & Fabien Ectors & , 2023. "Bitter taste cells in the ventricular walls of the murine brain regulate glucose homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Anna R. Smith & Fatima Rizvi & Elissa Everton & Anisah Adeagbo & Susan Wu & Ying Tam & Hiromi Muramatsu & Norbert Pardi & Drew Weissman & Valerie Gouon-Evans, 2024. "Transient growth factor expression via mRNA in lipid nanoparticles promotes hepatocyte cell therapy in mice," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    8. Yuki Takakura & Moeka Machida & Natsumi Terada & Yuka Katsumi & Seika Kawamura & Kenta Horie & Maki Miyauchi & Tatsuya Ishikawa & Nobuko Akiyama & Takao Seki & Takahisa Miyao & Mio Hayama & Rin Endo &, 2024. "Mitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity," Nature Communications, Nature, vol. 15(1), pages 1-19, 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_s41467-023-37589-4. 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.