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Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche

Author

Listed:
  • Manqiang Lin

    (Charité - Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Kimberly Hartl

    (Charité - Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Julian Heuberger

    (Charité - Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Giulia Beccaceci

    (Charité - Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Hilmar Berger

    (Charité - Universitätsmedizin Berlin)

  • Hao Li

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Lichao Liu

    (Charité - Universitätsmedizin Berlin)

  • Stefanie Müllerke

    (Charité - Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Thomas Conrad

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
    Berlin Institute of Health at Charité - Universitätsmedizin Berlin)

  • Felix Heymann

    (Charité - Universitätsmedizin Berlin)

  • Andrew Woehler

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Frank Tacke

    (Charité - Universitätsmedizin Berlin)

  • Nikolaus Rajewsky

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC))

  • Michael Sigal

    (Charité - Universitätsmedizin Berlin
    Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC))

Abstract

The cellular organization of gastrointestinal crypts is orchestrated by different cells of the stromal niche but available in vitro models fail to fully recapitulate the interplay between epithelium and stroma. Here, we establish a colon assembloid system comprising the epithelium and diverse stromal cell subtypes. These assembloids recapitulate the development of mature crypts resembling in vivo cellular diversity and organization, including maintenance of a stem/progenitor cell compartment in the base and their maturation into secretory/absorptive cell types. This process is supported by self-organizing stromal cells around the crypts that resemble in vivo organization, with cell types that support stem cell turnover adjacent to the stem cell compartment. Assembloids that lack BMP receptors either in epithelial or stromal cells fail to undergo proper crypt formation. Our data highlight the crucial role of bidirectional signaling between epithelium and stroma, with BMP as a central determinant of compartmentalization along the crypt axis.

Suggested Citation

  • Manqiang Lin & Kimberly Hartl & Julian Heuberger & Giulia Beccaceci & Hilmar Berger & Hao Li & Lichao Liu & Stefanie Müllerke & Thomas Conrad & Felix Heymann & Andrew Woehler & Frank Tacke & Nikolaus , 2023. "Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38780-3
    DOI: 10.1038/s41467-023-38780-3
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