IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms15380.html
   My bibliography  Save this article

Engineering the haemogenic niche mitigates endogenous inhibitory signals and controls pluripotent stem cell-derived blood emergence

Author

Listed:
  • Nafees Rahman

    (University of Toronto
    Institute of Biomaterials and Biomedical Engineering, University of Toronto)

  • Patrick M. Brauer

    (Biological Sciences, Sunnybrook Research Institute)

  • Lilian Ho

    (Life Sciences (Biochemistry), University of Waterloo)

  • Tatiana Usenko

    (Institute of Biomaterials and Biomedical Engineering, University of Toronto)

  • Mukul Tewary

    (Institute of Biomaterials and Biomedical Engineering, University of Toronto
    Collaborative Program in Developmental Biology, University of Toronto)

  • Juan Carlos Zúñiga-Pflücker

    (Biological Sciences, Sunnybrook Research Institute
    University of Toronto
    Medicine by Design, a Canada First Research Excellence Program at the University of Toronto)

  • Peter W. Zandstra

    (University of Toronto
    Institute of Biomaterials and Biomedical Engineering, University of Toronto
    Medicine by Design, a Canada First Research Excellence Program at the University of Toronto
    Terrence Donnelly Centre for Cellular & Biomolecular Research, University of Toronto)

Abstract

Efforts to recapitulate haematopoiesis, a process guided by spatial and temporal inductive signals, to generate haematopoietic progenitors from human pluripotent stem cells (hPSCs) have focused primarily on exogenous signalling pathway activation or inhibition. Here we show haemogenic niches can be engineered using microfabrication strategies by micropatterning hPSC-derived haemogenic endothelial (HE) cells into spatially-organized, size-controlled colonies. CD34+VECAD+ HE cells were generated with multi-lineage potential in serum-free conditions and cultured as size-specific haemogenic niches that displayed enhanced blood cell induction over non-micropatterned cultures. Intra-colony analysis revealed radial organization of CD34 and VECAD expression levels, with CD45+ blood cells emerging primarily from the colony centroid area. We identify the induced interferon gamma protein (IP-10)/p-38 MAPK signalling pathway as the mechanism for haematopoietic inhibition in our culture system. Our results highlight the role of spatial organization in hPSC-derived blood generation, and provide a quantitative platform for interrogating molecular pathways that regulate human haematopoiesis.

Suggested Citation

  • Nafees Rahman & Patrick M. Brauer & Lilian Ho & Tatiana Usenko & Mukul Tewary & Juan Carlos Zúñiga-Pflücker & Peter W. Zandstra, 2017. "Engineering the haemogenic niche mitigates endogenous inhibitory signals and controls pluripotent stem cell-derived blood emergence," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15380
    DOI: 10.1038/ncomms15380
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms15380
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms15380?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
    ---><---

    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:8:y:2017:i:1:d:10.1038_ncomms15380. 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.