IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-35965-8.html
   My bibliography  Save this article

Epithelial disruption drives mesendoderm differentiation in human pluripotent stem cells by enabling TGF-β protein sensing

Author

Listed:
  • Thomas Legier

    (NeuroMarseille)

  • Diane Rattier

    (NeuroMarseille)

  • Jack Llewellyn

    (NeuroMarseille)

  • Thomas Vannier

    (NeuroMarseille)

  • Benoit Sorre

    (Laboratoire Physico Chimie Curie)

  • Flavio Maina

    (NeuroMarseille)

  • Rosanna Dono

    (NeuroMarseille)

Abstract

The processes of primitive streak formation and fate specification in the mammalian epiblast rely on complex interactions between morphogens and tissue organization. Little is known about how these instructive cues functionally interact to regulate gastrulation. We interrogated the interplay between tissue organization and morphogens by using human induced pluripotent stem cells (hiPSCs) downregulated for the morphogen regulator GLYPICAN-4, in which defects in tight junctions result in areas of disrupted epithelial integrity. Remarkably, this phenotype does not affect hiPSC stemness, but impacts on cell fate acquisition. Strikingly, cells within disrupted areas become competent to perceive the gastrulation signals BMP4 and ACTIVIN A, an in vitro surrogate for NODAL, and thus differentiate into mesendoderm. Yet, disruption of epithelial integrity sustains activation of BMP4 and ACTIVIN A downstream effectors and correlates with enhanced hiPSC endoderm/mesoderm differentiation. Altogether, our results disclose epithelial integrity as a key determinant of TGF-β activity and highlight an additional mechanism guiding morphogen sensing and spatial cell fate change within an epithelium.

Suggested Citation

  • Thomas Legier & Diane Rattier & Jack Llewellyn & Thomas Vannier & Benoit Sorre & Flavio Maina & Rosanna Dono, 2023. "Epithelial disruption drives mesendoderm differentiation in human pluripotent stem cells by enabling TGF-β protein sensing," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35965-8
    DOI: 10.1038/s41467-023-35965-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-35965-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-35965-8?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. Zhechun Zhang & Steven Zwick & Ethan Loew & Joshua S. Grimley & Sharad Ramanathan, 2019. "Mouse embryo geometry drives formation of robust signaling gradients through receptor localization," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    2. Alessandro Fiorenzano & Emilia Pascale & Cristina D'Aniello & Dario Acampora & Cecilia Bassalert & Francesco Russo & Gennaro Andolfi & Mauro Biffoni & Federica Francescangeli & Ann Zeuner & Claudia An, 2016. "Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency," Nature Communications, Nature, vol. 7(1), pages 1-16, November.
    3. Innokenty Woichansky & Carlo Antonio Beretta & Nicola Berns & Veit Riechmann, 2016. "Three mechanisms control E-cadherin localization to the zonula adherens," Nature Communications, Nature, vol. 7(1), pages 1-11, April.
    4. Jane Brennan & Cindy C. Lu & Dominic P. Norris & Tristan A. Rodriguez & Rosa S. P. Beddington & Elizabeth J. Robertson, 2001. "Nodal signalling in the epiblast patterns the early mouse embryo," Nature, Nature, vol. 411(6840), pages 965-969, June.
    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. Haipeng Fu & Tingyu Wang & Xiaohui Kong & Kun Yan & Yang Yang & Jingyi Cao & Yafei Yuan & Nan Wang & Kehkooi Kee & Zhi John Lu & Qiaoran Xi, 2022. "A Nodal enhanced micropeptide NEMEP regulates glucose uptake during mesendoderm differentiation of embryonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Nicolas Allègre & Sabine Chauveau & Cynthia Dennis & Yoan Renaud & Dimitri Meistermann & Lorena Valverde Estrella & Pierre Pouchin & Michel Cohen-Tannoudji & Laurent David & Claire Chazaud, 2022. "NANOG initiates epiblast fate through the coordination of pluripotency genes expression," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Nabila Founounou & Reza Farhadifar & Giovanna M. Collu & Ursula Weber & Michael J. Shelley & Marek Mlodzik, 2021. "Tissue fluidity mediated by adherens junction dynamics promotes planar cell polarity-driven ommatidial rotation," Nature Communications, Nature, vol. 12(1), pages 1-16, 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_s41467-023-35965-8. 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.