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Cell-intrinsic Aryl Hydrocarbon Receptor signalling is required for the resolution of injury-induced colonic stem cells

Author

Listed:
  • Kathleen Shah

    (The Francis Crick Institute)

  • Muralidhara Rao Maradana

    (The Francis Crick Institute)

  • M. Joaquina Delàs

    (The Francis Crick Institute)

  • Amina Metidji

    (St Jude Children’s Hospital)

  • Frederike Graelmann

    (University of Bonn)

  • Miriam Llorian

    (The Francis Crick Institute)

  • Probir Chakravarty

    (The Francis Crick Institute)

  • Ying Li

    (The Francis Crick Institute)

  • Mauro Tolaini

    (The Francis Crick Institute)

  • Michael Shapiro

    (The Francis Crick Institute)

  • Gavin Kelly

    (The Francis Crick Institute)

  • Chris Cheshire

    (The Francis Crick Institute)

  • Deendyal Bhurta

    (CSIR - Indian Institute of Integrative Medicine)

  • Sandip B. Bharate

    (CSIR - Indian Institute of Integrative Medicine)

  • Brigitta Stockinger

    (The Francis Crick Institute)

Abstract

The aryl hydrocarbon receptor (AHR) is an environmental sensor that integrates microbial and dietary cues to influence physiological processes within the intestinal microenvironment, protecting against colitis and colitis-associated colorectal cancer development. Rapid tissue regeneration upon injury is important for the reinstatement of barrier integrity and its dysregulation promotes malignant transformation. Here we show that AHR is important for the termination of the regenerative response and the reacquisition of mature epithelial cell identity post injury in vivo and in organoid cultures in vitro. Using an integrative multi-omics approach in colon organoids, we show that AHR is required for timely termination of the regenerative response through direct regulation of transcription factors involved in epithelial cell differentiation as well as restriction of chromatin accessibility to regeneration-associated Yap/Tead transcriptional targets. Safeguarding a regulated regenerative response places AHR at a pivotal position in the delicate balance between controlled regeneration and malignant transformation.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29098-7
    DOI: 10.1038/s41467-022-29098-7
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    as
    1. Adam L. Haber & Moshe Biton & Noga Rogel & Rebecca H. Herbst & Karthik Shekhar & Christopher Smillie & Grace Burgin & Toni M. Delorey & Michael R. Howitt & Yarden Katz & Itay Tirosh & Semir Beyaz & Da, 2017. "A single-cell survey of the small intestinal epithelium," Nature, Nature, vol. 551(7680), pages 333-339, November.
    2. Mette Bentsen & Philipp Goymann & Hendrik Schultheis & Kathrin Klee & Anastasiia Petrova & René Wiegandt & Annika Fust & Jens Preussner & Carsten Kuenne & Thomas Braun & Johnny Kim & Mario Looso, 2020. "ATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic genome activation," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    3. Ilya Lukonin & Denise Serra & Ludivine Challet Meylan & Katrin Volkmann & Janine Baaten & Rui Zhao & Shelly Meeusen & Karyn Colman & Francisca Maurer & Michael B. Stadler & Jeremy Jenkins & Prisca Lib, 2020. "Phenotypic landscape of intestinal organoid regeneration," Nature, Nature, vol. 586(7828), pages 275-280, October.
    4. Ysbrand M. Nusse & Adam K. Savage & Pauline Marangoni & Axel K. M. Rosendahl-Huber & Tyler A. Landman & Frederic J. Sauvage & Richard M. Locksley & Ophir D. Klein, 2018. "Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche," Nature, Nature, vol. 559(7712), pages 109-113, July.
    5. Ysbrand M. Nusse & Adam K. Savage & Pauline Marangoni & Axel K. M. Rosendahl-Huber & Tyler A. Landman & Frederic J. Sauvage & Richard M. Locksley & Ophir D. Klein, 2018. "Publisher Correction: Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche," Nature, Nature, vol. 562(7727), pages 22-22, October.
    6. 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.
    7. Jeff Vierstra & John Lazar & Richard Sandstrom & Jessica Halow & Kristen Lee & Daniel Bates & Morgan Diegel & Douglas Dunn & Fidencio Neri & Eric Haugen & Eric Rynes & Alex Reynolds & Jemma Nelson & A, 2020. "Global reference mapping of human transcription factor footprints," Nature, Nature, vol. 583(7818), pages 729-736, July.
    8. Salvatore Simmini & Monika Bialecka & Meritxell Huch & Lennart Kester & Marc van de Wetering & Toshiro Sato & Felix Beck & Alexander van Oudenaarden & Hans Clevers & Jacqueline Deschamps, 2014. "Transformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
    9. Chris Schiering & Emma Wincent & Amina Metidji & Andrea Iseppon & Ying Li & Alexandre J. Potocnik & Sara Omenetti & Colin J. Henderson & C. Roland Wolf & Daniel W. Nebert & Brigitta Stockinger, 2017. "Feedback control of AHR signalling regulates intestinal immunity," Nature, Nature, vol. 542(7640), pages 242-245, February.
    10. Konrad Gronke & Pedro P. Hernández & Jakob Zimmermann & Christoph S. N. Klose & Michael Kofoed-Branzk & Fabian Guendel & Mario Witkowski & Caroline Tizian & Lukas Amann & Fabian Schumacher & Hansruedi, 2019. "Interleukin-22 protects intestinal stem cells against genotoxic stress," Nature, Nature, vol. 566(7743), pages 249-253, February.
    11. 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.
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    Cited by:

    1. Xiuchuan (Lucas) Hu & Wenfeng Xiao & Yuxian Lei & Adam Green & Xinyi Lee & Muralidhara Rao Maradana & Yajing Gao & Xueru Xie & Rui Wang & George Chennell & M. Albert Basson & Pete Kille & Wolfgang Mar, 2023. "Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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