IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms8739.html
   My bibliography  Save this article

Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition

Author

Listed:
  • Carlos O. Lizama

    (Cardiovascular Research Institute, University of California, San Francisco)

  • John S. Hawkins

    (Cardiovascular Research Institute, University of California, San Francisco)

  • Christopher E. Schmitt

    (Cardiovascular Research Institute, University of California, San Francisco)

  • Frank L. Bos

    (Cardiovascular Research Institute, University of California, San Francisco)

  • Joan P. Zape

    (Cardiovascular Research Institute, University of California, San Francisco)

  • Kelly M. Cautivo

    (Diabetes, and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile)

  • Hugo Borges Pinto

    (Burke Medical Research Institute
    Brain and Mind Research Institute, Weill Cornell Medical College
    Weill Cornell Medical College)

  • Alexander M. Rhyner

    (Baylor College of Medicine
    Cardiovascular Research Institute, Baylor College of Medicine)

  • Hui Yu

    (Cardiovascular Research Institute, University of California, San Francisco)

  • Mary E. Donohoe

    (Burke Medical Research Institute
    Brain and Mind Research Institute, Weill Cornell Medical College
    Weill Cornell Medical College)

  • Joshua D. Wythe

    (Baylor College of Medicine
    Cardiovascular Research Institute, Baylor College of Medicine)

  • Ann C. Zovein

    (Cardiovascular Research Institute, University of California, San Francisco
    School of Medicine, University of California, San Francisco)

Abstract

Changes in cell fate and identity are essential for endothelial-to-haematopoietic transition (EHT), an embryonic process that generates the first adult populations of haematopoietic stem cells (HSCs) from hemogenic endothelial cells. Dissecting EHT regulation is a critical step towards the production of in vitro derived HSCs. Yet, we do not know how distinct endothelial and haematopoietic fates are parsed during the transition. Here we show that genes required for arterial identity function later to repress haematopoietic fate. Tissue-specific, temporally controlled, genetic loss of arterial genes (Sox17 and Notch1) during EHT results in increased production of haematopoietic cells due to loss of Sox17-mediated repression of haematopoietic transcription factors (Runx1 and Gata2). However, the increase in EHT can be abrogated by increased Notch signalling. These findings demonstrate that the endothelial haematopoietic fate switch is actively repressed in a population of endothelial cells, and that derepression of these programs augments haematopoietic output.

Suggested Citation

  • Carlos O. Lizama & John S. Hawkins & Christopher E. Schmitt & Frank L. Bos & Joan P. Zape & Kelly M. Cautivo & Hugo Borges Pinto & Alexander M. Rhyner & Hui Yu & Mary E. Donohoe & Joshua D. Wythe & An, 2015. "Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8739
    DOI: 10.1038/ncomms8739
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms8739
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms8739?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. Brandon Hadland & Barbara Varnum-Finney & Stacey Dozono & Tessa Dignum & Cynthia Nourigat-McKay & Adam M. Heck & Takashi Ishida & Dana L. Jackson & Tomer Itkin & Jason M. Butler & Shahin Rafii & Cole , 2022. "Engineering a niche supporting hematopoietic stem cell development using integrated single-cell transcriptomics," 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:6:y:2015:i:1:d:10.1038_ncomms8739. 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.