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Cited by 286Wnt/β-catenin signaling in development and cancerDigestive system and related healthCancer Cells and Metastasis

PDGFRα + pericryptal stromal cells are the critical source of Wnts and RSPO3 for murine intestinal stem cells in vivo

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Greicius, Gediminas, Kabiri, Zahra, Sigmundsson, Kristmundur, Liang, Chao, Bunte, Ralph, Singh, Manvendra K., Virshup, David M.·2018·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1713510115PMC PMC5889626
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Abstract

Significance: Tissue stem cells in vivo reside in highly structured niches that provide signals for proliferation and differentiation. Understanding the role of the niche requires identifying the key cell types that provide these regulators. In the intestine, R-spondins and Wnts are essential regulators of the stem-cell niche. Here we identify subepithelial myofibroblasts of the PDGF receptor α lineage as the specific stromal cell type that secretes these ligands. These data demonstrate the close interaction between epithelial stem cells and the underlying regulatory stroma niche and provide insights into both normal homeostasis and tissue recovery after injury.

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  • RSPO3 emerged among the top-ten HSC ligands mediating HSC-hepatocyte interactions through its corresponding receptors LGR4 and LGR5.

    “RSPO3, a potent positive regulator of the WNT pathway21,22, emerged among the top-ten HSC ligands mediating HSC–hepatocyte interactions through its corresponding receptors LGR4 and LGR5 (Fig. 3b and Supplementary Table 4).”

    From Hepatic stellate cells control liver zonation, size and functions via R-spondin 3 (2025) · cites this paper as [21]

  • The findings provide evidence for a mesenchymal liver niche that controls epithelial cell functions in health and disease, akin to R-spondin-LGR5-mediated mesenchymal-epithelial cross-talk in the gastrointestinal tract.

    “Together, our findings provide evidence for a mesenchymal liver niche that controls epithelial cell functions in health and disease, akin to the R-spondin–LGR5-mediated mesenchymal–epithelial cross-talk in the gastrointestinal tract21,22.”

    From Hepatic stellate cells control liver zonation, size and functions via R-spondin 3 (2025) · cites this paper as [21]

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Sorted by citations

Authors
Greicius, G., Kabiri, Z., Sigmundsson, K., Liang, C., Bunte, R., Singh, M. K., & Virshup, D. M.
Affiliations
National University of Singapore (SG)
Corresponding author
Virshup, David M.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2018-03-20
Volume
115
Issue
14
Pages
E3173-E3181
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1713510115
PMC
PMC5889626
OpenAlex
W2793308128
Cited by
286
References
3
Citations by year
2026: 15 · 2025: 22 · 2024: 29 · 2023: 33 · 2022: 51 · 2021: 52 · 2020: 43 · 2019: 24 · 2018: 17
FWCI
12.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
Funders
  • MOH | National Medical Research Council (STaR 913-301-006-213)
  • Agency for Science, Technology and Research (BMRC 13/1/96/19/690)
  • National Research Foundation Singapore (NRFF2016)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
intestinal stem cells, PDGF receptor alpha, subepithelial myofibroblasts, Wnt signaling, RSPO3, stem cell niche, stromal-epithelial interactions, intestinal homeostasis
MeSH terms
Acyltransferases, Animals, Cell Differentiation, Epithelial Cells, Homeostasis, Intestinal Mucosa, Intestines, Membrane Proteins, Mice, Inbred C57BL, Organoids, Stem Cells, Stromal Cells, Mice, Knockout, Thrombospondins, Receptor, Platelet-Derived Growth Factor alpha, Cell Proliferation, Wnt1 Protein, Mice, Stem Cell Niche

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