Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches

Nat Commun. 2020 Jan 17;11(1):334. doi: 10.1038/s41467-019-14058-5.

Abstract

Stomach and intestinal stem cells are located in discrete niches called the isthmus and crypt, respectively. Recent studies have demonstrated a surprisingly conserved role for Wnt signaling in gastrointestinal development. Although intestinal stromal cells secrete Wnt ligands to promote stem cell renewal, the source of stomach Wnt ligands is still unclear. Here, by performing single cell analysis, we identify gastrointestinal stromal cell populations with transcriptome signatures that are conserved between the stomach and intestine. In close proximity to epithelial cells, these perictye-like cells highly express telocyte and pericyte markers as well as Wnt ligands, and they are enriched for Hh signaling. By analyzing mice activated for Hh signaling, we show a conserved mechanism of GLI2 activation of Wnt ligands. Moreover, genetic inhibition of Wnt secretion in perictye-like stromal cells or stromal cells more broadly demonstrates their essential roles in gastrointestinal regeneration and development, respectively, highlighting a redundancy in gastrointestinal stem cell niches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Self Renewal / genetics
  • Epithelial Cells / metabolism
  • Gastrointestinal Tract / cytology
  • Gastrointestinal Tract / metabolism*
  • Genetic Testing*
  • Homeostasis
  • Ligands
  • Male
  • Mice
  • Mice, Knockout
  • Regeneration
  • Stem Cell Niche / genetics*
  • Stromal Cells / cytology
  • Stromal Cells / metabolism*
  • Telocytes / metabolism
  • Transcriptome
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway
  • Zinc Finger Protein Gli2 / metabolism

Substances

  • Gli2 protein, mouse
  • Ligands
  • Wnt Proteins
  • Zinc Finger Protein Gli2

Grants and funding