IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38780-3.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38780-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38780-3?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. Michal Shoshkes-Carmel & Yue J. Wang & Kirk J. Wangensteen & Beáta Tóth & Ayano Kondo & Efi E. Massasa & Shalev Itzkovitz & Klaus H. Kaestner, 2018. "Subepithelial telocytes are an important source of Wnts that supports intestinal crypts," Nature, Nature, vol. 557(7704), pages 242-246, May.
    2. Toshiro Sato & Robert G. Vries & Hugo J. Snippert & Marc van de Wetering & Nick Barker & Daniel E. Stange & Johan H. van Es & Arie Abo & Pekka Kujala & Peter J. Peters & Hans Clevers, 2009. "Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche," Nature, Nature, vol. 459(7244), pages 262-265, May.
    3. Michael Sigal & Catriona Y. Logan & Marta Kapalczynska & Hans-Joachim Mollenkopf & Hilmar Berger & Bertram Wiedenmann & Roeland Nusse & Manuel R. Amieva & Thomas F. Meyer, 2017. "Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis," Nature, Nature, vol. 548(7668), pages 451-455, August.
    4. Christine Harnack & Hilmar Berger & Agne Antanaviciute & Ramon Vidal & Sascha Sauer & Alison Simmons & Thomas F. Meyer & Michael Sigal, 2019. "R-spondin 3 promotes stem cell recovery and epithelial regeneration in the colon," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    5. Marta Kapalczynska & Manqiang Lin & Jeroen Maertzdorf & Julian Heuberger & Stefanie Muellerke & Xiangsheng Zuo & Ramon Vidal & Imad Shureiqi & Anne-Sophie Fischer & Sascha Sauer & Hilmar Berger & Evel, 2022. "BMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    6. Michal Shoshkes-Carmel & Yue J. Wang & Kirk J. Wangensteen & Beáta Tóth & Ayano Kondo & Efi E. Massasa & Shalev Itzkovitz & Klaus H. Kaestner, 2018. "Author Correction: Subepithelial telocytes are an important source of Wnts that supports intestinal crypts," Nature, Nature, vol. 560(7718), pages 29-29, August.
    7. Kaushal Parikh & Agne Antanaviciute & David Fawkner-Corbett & Marta Jagielowicz & Anna Aulicino & Christoffer Lagerholm & Simon Davis & James Kinchen & Hannah H. Chen & Nasullah Khalid Alham & Neil As, 2019. "Colonic epithelial cell diversity in health and inflammatory bowel disease," Nature, Nature, vol. 567(7746), pages 49-55, March.
    8. Eunjee Kim & Seoyoung Choi & Byunghee Kang & JungHo Kong & Yubin Kim & Woong Hee Yoon & Hwa-Rim Lee & SungEun Kim & Hyo-Min Kim & HyeSun Lee & Chorong Yang & You Jeong Lee & Minyong Kang & Tae-Young R, 2020. "Creation of bladder assembloids mimicking tissue regeneration and cancer," Nature, Nature, vol. 588(7839), pages 664-669, December.
    9. Alex Gregorieff & Yu Liu & Mohammad R. Inanlou & Yuliya Khomchuk & Jeffrey L. Wrana, 2015. "Yap-dependent reprogramming of Lgr5+ stem cells drives intestinal regeneration and cancer," Nature, Nature, vol. 526(7575), pages 715-718, October.
    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. Mara Martín-Alonso & Sharif Iqbal & Pia M. Vornewald & Håvard T. Lindholm & Mirjam J. Damen & Fernando Martínez & Sigrid Hoel & Alberto Díez-Sánchez & Maarten Altelaar & Pekka Katajisto & Alicia G. Ar, 2021. "Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    2. Elisa Manieri & Guodong Tie & Ermanno Malagola & Davide Seruggia & Shariq Madha & Adrianna Maglieri & Kun Huang & Yuko Fujiwara & Kevin Zhang & Stuart H. Orkin & Timothy C. Wang & Ruiyang He & Neil Mc, 2023. "Role of PDGFRA+ cells and a CD55+ PDGFRALo fraction in the gastric mesenchymal niche," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Liang Yang & Zifeng Ruan & Xiaobing Lin & Hao Wang & Yanmin Xin & Haite Tang & Zhijuan Hu & Yunhao Zhou & Yi Wu & Junwei Wang & Dajiang Qin & Gang Lu & Kerry M. Loomes & Wai-Yee Chan & Xingguo Liu, 2024. "NAD+ dependent UPRmt activation underlies intestinal aging caused by mitochondrial DNA mutations," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Martti Maimets & Marianne Terndrup Pedersen & Jordi Guiu & Jes Dreier & Malte Thodberg & Yasuko Antoku & Pawel J. Schweiger & Leonor Rib & Raul Bardini Bressan & Yi Miao & K. Christopher Garcia & Albi, 2022. "Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. 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.
    6. Clara Morral & Arshad Ayyaz & Hsuan-Cheng Kuo & Mardi Fink & Ioannis I. Verginadis & Andrea R. Daniel & Danielle N. Burner & Lucy M. Driver & Sloane Satow & Stephanie Hasapis & Reem Ghinnagow & Lixia , 2024. "p53 promotes revival stem cells in the regenerating intestine after severe radiation injury," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Marco Calafiore & Ya-Yuan Fu & Paola Vinci & Viktor Arnhold & Winston Y. Chang & Suze A. Jansen & Anastasiya Egorova & Shuichiro Takashima & Jason Kuttiyara & Takahiro Ito & Jonathan Serody & Susumu N, 2023. "A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Jong Hoon Won & Jacob S. Choi & Joon-Il Jun, 2022. "CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. Simone Isling Pærregaard & Line Wulff & Sophie Schussek & Kristoffer Niss & Urs Mörbe & Johan Jendholm & Kerstin Wendland & Anna T. Andrusaite & Kevin F. Brulois & Robert J. B. Nibbs & Katarzyna Sitni, 2023. "The small and large intestine contain related mesenchymal subsets that derive from embryonic Gli1+ precursors," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Marta Kapalczynska & Manqiang Lin & Jeroen Maertzdorf & Julian Heuberger & Stefanie Muellerke & Xiangsheng Zuo & Ramon Vidal & Imad Shureiqi & Anne-Sophie Fischer & Sascha Sauer & Hilmar Berger & Evel, 2022. "BMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    11. Jeremiah Bernier-Latmani & Cristina Mauri & Rachel Marcone & François Renevey & Stephan Durot & Liqun He & Michael Vanlandewijck & Catherine Maclachlan & Suzel Davanture & Nicola Zamboni & Graham W. K, 2022. "ADAMTS18+ villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    12. Ryan J. Smith & Minggao Liang & Adrian Kwan Ho Loe & Theodora Yung & Ji-Eun Kim & Matthew Hudson & Michael D. Wilson & Tae-Hee Kim, 2023. "Epigenetic control of cellular crosstalk defines gastrointestinal organ fate and function," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    13. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    14. Suran Kim & Sungjin Min & Yi Sun Choi & Sung-Hyun Jo & Jae Hun Jung & Kyusun Han & Jin Kim & Soohwan An & Yong Woo Ji & Yun-Gon Kim & Seung-Woo Cho, 2022. "Tissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    15. Shuting Li & Chia-Wen Lu & Elia C. Diem & Wang Li & Melanie Guderian & Marc Lindenberg & Friederike Kruse & Manuela Buettner & Stefan Floess & Markus R. Winny & Robert Geffers & Hans-Hermann Richnow &, 2022. "Acetyl-CoA-Carboxylase 1-mediated de novo fatty acid synthesis sustains Lgr5+ intestinal stem cell function," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    16. Laura Solé & Teresa Lobo-Jarne & Daniel Álvarez-Villanueva & Josune Alonso-Marañón & Yolanda Guillén & Marta Guix & Irene Sangrador & Catalina Rozalén & Anna Vert & Antonio Barbachano & Joan Lop & Mar, 2022. "p53 wild-type colorectal cancer cells that express a fetal gene signature are associated with metastasis and poor prognosis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    17. Wenjuan Zhang & Bowei Zhou & Xiao Yang & Jin Zhao & Jingjuan Hu & Yuqi Ding & Shuteng Zhan & Yifeng Yang & Jun Chen & Fu Zhang & Bingcheng Zhao & Fan Deng & Zebin Lin & Qishun Sun & Fangling Zhang & Z, 2023. "Exosomal circEZH2_005, an intestinal injury biomarker, alleviates intestinal ischemia/reperfusion injury by mediating Gprc5a signaling," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    18. Cezanne Miete & Gonzalo P. Solis & Alexey Koval & Martina Brückner & Vladimir L. Katanaev & Jürgen Behrens & Dominic B. Bernkopf, 2022. "Gαi2-induced conductin/axin2 condensates inhibit Wnt/β-catenin signaling and suppress cancer growth," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    19. Anna Urciuolo & Giovanni Giuseppe Giobbe & Yixiao Dong & Federica Michielin & Luca Brandolino & Michael Magnussen & Onelia Gagliano & Giulia Selmin & Valentina Scattolini & Paolo Raffa & Paola Caccin , 2023. "Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    20. María A. Duque-Correa & David Goulding & Faye H. Rodgers & J. Andrew Gillis & Claire Cormie & Kate A. Rawlinson & Allison J. Bancroft & Hayley M. Bennett & Magda E. Lotkowska & Adam J. Reid & Annelies, 2022. "Defining the early stages of intestinal colonisation by whipworms," Nature Communications, Nature, vol. 13(1), pages 1-15, 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_s41467-023-38780-3. 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.