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Self-organization and symmetry breaking in intestinal organoid development

Author

Listed:
  • Denise Serra

    (Friedrich Miescher Institute for Biomedical Research (FMI)
    University of Basel)

  • Urs Mayr

    (Friedrich Miescher Institute for Biomedical Research (FMI)
    University of Basel)

  • Andrea Boni

    (Friedrich Miescher Institute for Biomedical Research (FMI)
    Viventis Microscopy Sàrl, EPFL Innovation Park)

  • Ilya Lukonin

    (Friedrich Miescher Institute for Biomedical Research (FMI)
    University of Basel)

  • Markus Rempfler

    (Friedrich Miescher Institute for Biomedical Research (FMI))

  • Ludivine Challet Meylan

    (Friedrich Miescher Institute for Biomedical Research (FMI))

  • Michael B. Stadler

    (Friedrich Miescher Institute for Biomedical Research (FMI)
    Swiss Institute of Bioinformatics)

  • Petr Strnad

    (Friedrich Miescher Institute for Biomedical Research (FMI)
    Viventis Microscopy Sàrl, EPFL Innovation Park)

  • Panagiotis Papasaikas

    (Friedrich Miescher Institute for Biomedical Research (FMI)
    Swiss Institute of Bioinformatics)

  • Dario Vischi

    (Friedrich Miescher Institute for Biomedical Research (FMI))

  • Annick Waldt

    (Novartis Pharma AG)

  • Guglielmo Roma

    (Novartis Pharma AG)

  • Prisca Liberali

    (Friedrich Miescher Institute for Biomedical Research (FMI)
    University of Basel)

Abstract

Intestinal organoids are complex three-dimensional structures that mimic the cell-type composition and tissue organization of the intestine by recapitulating the self-organizing ability of cell populations derived from a single intestinal stem cell. Crucial in this process is a first symmetry-breaking event, in which only a fraction of identical cells in a symmetrical sphere differentiate into Paneth cells, which generate the stem-cell niche and lead to asymmetric structures such as the crypts and villi. Here we combine single-cell quantitative genomic and imaging approaches to characterize the development of intestinal organoids from single cells. We show that their development follows a regeneration process that is driven by transient activation of the transcriptional regulator YAP1. Cell-to-cell variability in YAP1, emerging in symmetrical spheres, initiates Notch and DLL1 activation, and drives the symmetry-breaking event and formation of the first Paneth cell. Our findings reveal how single cells exposed to a uniform growth-promoting environment have the intrinsic ability to generate emergent, self-organized behaviour that results in the formation of complex multicellular asymmetric structures.

Suggested Citation

  • Denise Serra & Urs Mayr & Andrea Boni & Ilya Lukonin & Markus Rempfler & Ludivine Challet Meylan & Michael B. Stadler & Petr Strnad & Panagiotis Papasaikas & Dario Vischi & Annick Waldt & Guglielmo Ro, 2019. "Self-organization and symmetry breaking in intestinal organoid development," Nature, Nature, vol. 569(7754), pages 66-72, May.
  • Handle: RePEc:nat:nature:v:569:y:2019:i:7754:d:10.1038_s41586-019-1146-y
    DOI: 10.1038/s41586-019-1146-y
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    Cited by:

    1. Jina Yun & Simon Hansen & Otto Morris & David T. Madden & Clare Peters Libeu & Arjun J. Kumar & Cameron Wehrfritz & Aaron H. Nile & Yingnan Zhang & Lijuan Zhou & Yuxin Liang & Zora Modrusan & Michelle, 2023. "Senescent cells perturb intestinal stem cell differentiation through Ptk7 induced noncanonical Wnt and YAP signaling," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Johannes Betge & Niklas Rindtorff & Jan Sauer & Benedikt Rauscher & Clara Dingert & Haristi Gaitantzi & Frank Herweck & Kauthar Srour-Mhanna & Thilo Miersch & Erica Valentini & Kim E. Boonekamp & Vero, 2022. "The drug-induced phenotypic landscape of colorectal cancer organoids," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Gustavo Medeiros & Raphael Ortiz & Petr Strnad & Andrea Boni & Franziska Moos & Nicole Repina & Ludivine Challet Meylan & Francisca Maurer & Prisca Liberali, 2022. "Multiscale light-sheet organoid imaging framework," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Yi Liu & Efren Reyes & David Castillo-Azofeifa & Ophir D. Klein & Todd Nystul & Diane L. Barber, 2023. "Intracellular pH dynamics regulates intestinal stem cell lineage specification," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Kathleen Shah & Muralidhara Rao Maradana & M. Joaquina Delàs & Amina Metidji & Frederike Graelmann & Miriam Llorian & Probir Chakravarty & Ying Li & Mauro Tolaini & Michael Shapiro & Gavin Kelly & Chr, 2022. "Cell-intrinsic Aryl Hydrocarbon Receptor signalling is required for the resolution of injury-induced colonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Gawoon Shim & Isaac B. Breinyn & Alejandro Martínez-Calvo & Sameeksha Rao & Daniel J. Cohen, 2024. "Bioelectric stimulation controls tissue shape and size," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Sefora Conti & Valeria Venturini & Adrià Cañellas-Socias & Carme Cortina & Juan F. Abenza & Camille Stephan-Otto Attolini & Emily Middendorp Guerra & Catherine K. Xu & Jia Hui Li & Leone Rossetti & Gi, 2024. "Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Tom Brandstätter & David B. Brückner & Yu Long Han & Ricard Alert & Ming Guo & Chase P. Broedersz, 2023. "Curvature induces active velocity waves in rotating spherical tissues," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    9. Eva C. Freckmann & Emma Sandilands & Erin Cumming & Matthew Neilson & Alvaro Román-Fernández & Konstantina Nikolatou & Marisa Nacke & Tamsin R. M. Lannagan & Ann Hedley & David Strachan & Mark Salji &, 2022. "Traject3d allows label-free identification of distinct co-occurring phenotypes within 3D culture by live imaging," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    10. Wendy Xueyi Wang & Julie L. Lefebvre, 2022. "Morphological pseudotime ordering and fate mapping reveal diversification of cerebellar inhibitory interneurons," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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