IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v576y2019i7786d10.1038_s41586-019-1790-2.html
   My bibliography  Save this article

MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment

Author

Listed:
  • Vincenzo Calvanese

    (University of California Los Angeles
    University of California Los Angeles)

  • Andrew T. Nguyen

    (University of California Los Angeles)

  • Timothy J. Bolan

    (University of California Los Angeles)

  • Anastasia Vavilina

    (University of California Los Angeles)

  • Trent Su

    (University of California Los Angeles)

  • Lydia K. Lee

    (University of California Los Angeles)

  • Yanling Wang

    (University of California Los Angeles)

  • Fides D. Lay

    (University of California Los Angeles)

  • Mattias Magnusson

    (University of California Los Angeles
    University of California Los Angeles)

  • Gay M. Crooks

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Siavash K. Kurdistani

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Hanna K. A. Mikkola

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

Abstract

Limited knowledge of the mechanisms that govern the self-renewal of human haematopoietic stem cells (HSCs), and why this fails in culture, have impeded the expansion of HSCs for transplantation1. Here we identify MLLT3 (also known as AF9) as a crucial regulator of HSCs that is highly enriched in human fetal, neonatal and adult HSCs, but downregulated in culture. Depletion of MLLT3 prevented the maintenance of transplantable human haematopoietic stem or progenitor cells (HSPCs) in culture, whereas stabilizing MLLT3 expression in culture enabled more than 12-fold expansion of transplantable HSCs that provided balanced multilineage reconstitution in primary and secondary mouse recipients. Similar to endogenous MLLT3, overexpressed MLLT3 localized to active promoters in HSPCs, sustained levels of H3K79me2 and protected the HSC transcriptional program in culture. MLLT3 thus acts as HSC maintenance factor that links histone reader and modifying activities to modulate HSC gene expression, and may provide a promising approach to expand HSCs for transplantation.

Suggested Citation

  • Vincenzo Calvanese & Andrew T. Nguyen & Timothy J. Bolan & Anastasia Vavilina & Trent Su & Lydia K. Lee & Yanling Wang & Fides D. Lay & Mattias Magnusson & Gay M. Crooks & Siavash K. Kurdistani & Hann, 2019. "MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment," Nature, Nature, vol. 576(7786), pages 281-286, December.
    • Handle: RePEc:nat:nature:v:576:y:2019:i:7786:d:10.1038_s41586-019-1790-2
    DOI: 10.1038/s41586-019-1790-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-019-1790-2
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-019-1790-2?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Shicheng Sun & Ali Motazedian & Jacky Y. Li & Kevin Wijanarko & Joe Jiang Zhu & Kothila Tharmarajah & Kathleen A. Strumila & Anton Shkaruta & L. Rayburn Nigos & Jacqueline V. Schiesser & Yi Yu & Paul , 2024. "Efficient generation of human NOTCH ligand-expressing haemogenic endothelial cells as infrastructure for in vitro haematopoiesis and lymphopoiesis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Yosuke Komata & Akinori Kanai & Takahiro Maeda & Toshiya Inaba & Akihiko Yokoyama, 2023. "MOZ/ENL complex is a recruiting factor of leukemic AF10 fusion proteins," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Matteo Maria Naldini & Gabriele Casirati & Matteo Barcella & Paola Maria Vittoria Rancoita & Andrea Cosentino & Carolina Caserta & Francesca Pavesi & Erika Zonari & Giacomo Desantis & Diego Gilioli & , 2023. "Longitudinal single-cell profiling of chemotherapy response in acute myeloid leukemia," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. 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:nature:v:576:y:2019:i:7786:d:10.1038_s41586-019-1790-2. 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.