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Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
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Gut microbiota promotes stem cell differentiation through macrophage and mesenchymal niches in early postnatal

Ji-Eun Kim1, Bo Li2, Lijiang Fei3

  • 1Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.

Immunity
|December 6, 2022
PubMed

Insights

Early life gut microbes are crucial for intestinal stem cell development. Disrupting this microbial exposure impairs stem cell differentiation and is linked to necrotizing enterocolitis (NEC), but probiotics can help.

Area of Science:

  • Developmental biology
  • Microbiology
  • Gastroenterology

Background:

  • Intestinal stem cell maturation is influenced by gut microbiota after birth.
  • Early life microbial disruption can negatively impact intestinal development.

Purpose of the Study:

  • To investigate how early life microbial exposure affects the intestinal stem cell niche.
  • To understand the mechanisms by which microbiota regulate stem cell differentiation and niche maintenance.

Main Methods:

  • Single-cell transcriptional analysis of intestinal cells.
  • Mouse genetic models and organoid co-culture experiments.
  • Investigating the role of CD206+ macrophages and Wnt ligands.

Main Results:

  • Antibiotic treatment in early life impaired Paneth cell differentiation and macrophage specification.
  • A CD206+ macrophage subset secreted Wnt ligands, maintaining mesenchymal niche cells for Paneth cell differentiation.
  • Lactobacillus colonization or CD206+ macrophage transfer reduced necrotizing enterocolitis (NEC) severity.

Conclusions:

  • Gut microbiota critically regulate intestinal stem cell niches during early postnatal development.
  • Microbiota-derived signals, particularly from CD206+ macrophages, are essential for Paneth cell differentiation.
  • Targeting the microbiota or specific immune cells may offer therapeutic strategies for NEC.

Keywords:
Paneth cellsWnt signalingantibioticsintestinemacrophagesmicrobiotanecrotizing enterocolitisstem cell niche

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