IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43619-y.html
   My bibliography  Save this article

Role of PDGFRA+ cells and a CD55+ PDGFRALo fraction in the gastric mesenchymal niche

Author

Listed:
  • Elisa Manieri

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Guodong Tie

    (Dana-Farber Cancer Institute)

  • Ermanno Malagola

    (Columbia University Medical Center)

  • Davide Seruggia

    (Boston Children’s Hospital
    St. Anna Children’s Cancer Research Institute
    CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Shariq Madha

    (Dana-Farber Cancer Institute)

  • Adrianna Maglieri

    (Dana-Farber Cancer Institute)

  • Kun Huang

    (Dana-Farber Cancer Institute)

  • Yuko Fujiwara

    (Boston Children’s Hospital
    Howard Hughes Medical Institute)

  • Kevin Zhang

    (Boston Children’s Hospital)

  • Stuart H. Orkin

    (Boston Children’s Hospital
    Howard Hughes Medical Institute
    Harvard Stem Cell Institute)

  • Timothy C. Wang

    (Columbia University Medical Center)

  • Ruiyang He

    (Dana-Farber Cancer Institute)

  • Neil McCarthy

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Ramesh A. Shivdasani

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Harvard Stem Cell Institute)

Abstract

PDGFRA-expressing mesenchyme supports intestinal stem cells. Stomach epithelia have related niche dependencies, but their enabling mesenchymal cell populations are unknown, in part because previous studies pooled the gastric antrum and corpus. Our high-resolution imaging, transcriptional profiling, and organoid assays identify regional subpopulations and supportive capacities of purified mouse corpus and antral PDGFRA+ cells. Sub-epithelial PDGFRAHi myofibroblasts are principal sources of BMP ligands and two molecularly distinct pools distribute asymmetrically along antral glands but together fail to support epithelial growth in vitro. In contrast, PDGFRALo CD55+ cells strategically positioned beneath gastric glands promote epithelial expansion in the absence of other cells or factors. This population encompasses a small fraction expressing the BMP antagonist Grem1. Although Grem1+ cell ablation in vivo impairs intestinal stem cells, gastric stem cells are spared, implying that CD55+ cell activity in epithelial self-renewal derives from other subpopulations. Our findings shed light on spatial, molecular, and functional organization of gastric mesenchyme and the spectrum of signaling sources for epithelial support.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43619-y
    DOI: 10.1038/s41467-023-43619-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43619-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43619-y?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. Bahar Degirmenci & Tomas Valenta & Slavica Dimitrieva & George Hausmann & Konrad Basler, 2018. "GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells," Nature, Nature, vol. 558(7710), pages 449-453, June.
    4. Hitomi Takada & Yohei Sasagawa & Mika Yoshimura & Kaori Tanaka & Yoshimi Iwayama & Tetsutaro Hayashi & Ayako Isomura-Matoba & Itoshi Nikaido & Akira Kurisaki, 2023. "Author Correction: Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-1, December.
    5. 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.
    6. Nick Barker & Johan H. van Es & Jeroen Kuipers & Pekka Kujala & Maaike van den Born & Miranda Cozijnsen & Andrea Haegebarth & Jeroen Korving & Harry Begthel & Peter J. Peters & Hans Clevers, 2007. "Identification of stem cells in small intestine and colon by marker gene Lgr5," Nature, Nature, vol. 449(7165), pages 1003-1007, October.
    7. 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.
    8. Si Hui Tan & Yada Swathi & Shawna Tan & Jasmine Goh & Ryo Seishima & Kazuhiro Murakami & Masanobu Oshima & Toshikatsu Tsuji & Phyllis Phuah & Liang Thing Tan & Esther Wong & Aliya Fatehullah & Taotao , 2020. "AQP5 enriches for stem cells and cancer origins in the distal stomach," Nature, Nature, vol. 578(7795), pages 437-443, February.
    9. Hitomi Takada & Yohei Sasagawa & Mika Yoshimura & Kaori Tanaka & Yoshimi Iwayama & Tetsutaro Hayashi & Ayako Isomura-Matoba & Itoshi Nikaido & Akira Kurisaki, 2023. "Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Ji-Eun Kim & Lijiang Fei & Wen-Chi Yin & Sabrina Coquenlorge & Abilasha Rao-Bhatia & Xiaoyun Zhang & Sammy Shun Wai Shi & Ju Hee Lee & Noah A. Hahn & Wasi Rizvi & Kyoung-Han Kim & Hoon-Ki Sung & Chi-c, 2020. "Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    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. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    10. 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.
    11. Shamir Montazid & Sheila Bandyopadhyay & Daniel W. Hart & Nan Gao & Brian Johnson & Sri G. Thrumurthy & Dustin J. Penn & Bettina Wernisch & Mukesh Bansal & Philipp M. Altrock & Fabian Rost & Patrycja , 2023. "Adult stem cell activity in naked mole rats for long-term tissue maintenance," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    12. Tsunaki Higa & Yasutaka Okita & Akinobu Matsumoto & Shogo Nakayama & Takeru Oka & Osamu Sugahara & Daisuke Koga & Shoichiro Takeishi & Hirokazu Nakatsumi & Naoki Hosen & Sylvie Robine & Makoto M. Take, 2022. "Spatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    13. 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.
    14. 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.
    15. 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.
    16. Naveen Kumar & Pon Ganish Prakash & Christian Wentland & Shilpa Mary Kurian & Gaurav Jethva & Volker Brinkmann & Hans-Joachim Mollenkopf & Tobias Krammer & Christophe Toussaint & Antoine-Emmanuel Sali, 2024. "Decoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    17. Joana Silva & Ferhat Alkan & Sofia Ramalho & Goda Snieckute & Stefan Prekovic & Ana Krotenberg Garcia & Santiago Hernández-Pérez & Rob Kammen & Danielle Barnum & Liesbeth Hoekman & Maarten Altelaar & , 2022. "Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    18. 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.
    19. Yael Korem & Pablo Szekely & Yuval Hart & Hila Sheftel & Jean Hausser & Avi Mayo & Michael E Rothenberg & Tomer Kalisky & Uri Alon, 2015. "Geometry of the Gene Expression Space of Individual Cells," PLOS Computational Biology, Public Library of Science, vol. 11(7), pages 1-27, July.
    20. Qing Chen & Xin Zhang & Wei-Min Li & Yu-Qiang Ji & Hao-Zhe Cao & Pengsheng Zheng, 2014. "Prognostic Value of LGR5 in Colorectal Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-9, September.

    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_s41467-023-43619-y. 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.