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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
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