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

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 McCarthy and Ramesh A. Shivdasani ()
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Elisa Manieri: Dana-Farber Cancer Institute
Guodong Tie: Dana-Farber Cancer Institute
Ermanno Malagola: Columbia University Medical Center
Davide Seruggia: Boston Children’s Hospital
Shariq Madha: Dana-Farber Cancer Institute
Adrianna Maglieri: Dana-Farber Cancer Institute
Kun Huang: Dana-Farber Cancer Institute
Yuko Fujiwara: Boston Children’s Hospital
Kevin Zhang: Boston Children’s Hospital
Stuart H. Orkin: Boston Children’s Hospital
Timothy C. Wang: Columbia University Medical Center
Ruiyang He: Dana-Farber Cancer Institute
Neil McCarthy: Dana-Farber Cancer Institute
Ramesh A. Shivdasani: Dana-Farber Cancer Institute

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43619-y

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