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

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Item Type:Article
Title:Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche
Creators Name:Lin, M. and Hartl, K. and Heuberger, J. and Beccaceci, G. and Berger, H. and Li, H. and Liu, L. and Müllerke, S. and Conrad, T. and Heymann, F. and Woehler, A. and Tacke, F. and Rajewsky, N. and Sigal, M.
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.
Keywords:Cell Differentiation, Gastrointestinal Tract, Intestinal Mucosa, Signal Transduction, Stem Cells
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:14
Number:1
Page Range:3025
Date:25 May 2023
Official Publication:https://doi.org/10.1038/s41467-023-38780-3
PubMed:View item in PubMed

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