IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-22813-w.html
   My bibliography  Save this article

LRIG1 is a gatekeeper to exit from quiescence in adult neural stem cells

Author

Listed:
  • María Ángeles Marqués-Torrejón

    (University of Edinburgh)

  • Charles A. C. Williams

    (University of Edinburgh)

  • Benjamin Southgate

    (University of Edinburgh)

  • Neza Alfazema

    (University of Edinburgh)

  • Melanie P. Clements

    (University College London)

  • Claudia Garcia-Diaz

    (University College London)

  • Carla Blin

    (University of Edinburgh)

  • Nerea Arranz-Emparan

    (University of Edinburgh)

  • Jane Fraser

    (University of Edinburgh)

  • Noor Gammoh

    (University of Edinburgh)

  • Simona Parrinello

    (University College London)

  • Steven M. Pollard

    (University of Edinburgh)

Abstract

Adult neural stem cells (NSCs) must tightly regulate quiescence and proliferation. Single-cell analysis has suggested a continuum of cell states as NSCs exit quiescence. Here we capture and characterize in vitro primed quiescent NSCs and identify LRIG1 as an important regulator. We show that BMP-4 signaling induces a dormant non-cycling quiescent state (d-qNSCs), whereas combined BMP-4/FGF-2 signaling induces a distinct primed quiescent state poised for cell cycle re-entry. Primed quiescent NSCs (p-qNSCs) are defined by high levels of LRIG1 and CD9, as well as an interferon response signature, and can efficiently engraft into the adult subventricular zone (SVZ) niche. Genetic disruption of Lrig1 in vivo within the SVZ NSCs leads an enhanced proliferation. Mechanistically, LRIG1 primes quiescent NSCs for cell cycle re-entry and EGFR responsiveness by enabling EGFR protein levels to increase but limiting signaling activation. LRIG1 is therefore an important functional regulator of NSC exit from quiescence.

Suggested Citation

  • María Ángeles Marqués-Torrejón & Charles A. C. Williams & Benjamin Southgate & Neza Alfazema & Melanie P. Clements & Claudia Garcia-Diaz & Carla Blin & Nerea Arranz-Emparan & Jane Fraser & Noor Gammoh, 2021. "LRIG1 is a gatekeeper to exit from quiescence in adult neural stem cells," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22813-w
    DOI: 10.1038/s41467-021-22813-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-22813-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-22813-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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Ting Zhao & Yan Hong & Bowen Yan & Suming Huang & Guo-li Ming & Hongjun Song, 2024. "Epigenetic maintenance of adult neural stem cell quiescence in the mouse hippocampus via Setd1a," Nature Communications, Nature, vol. 15(1), pages 1-15, 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:12:y:2021:i:1:d:10.1038_s41467-021-22813-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.

    We have no bibliographic references for this item. You can help adding them by using 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.