Notch signaling regulates gastric antral LGR5 stem cell function

Area of Science:

• Gastroenterology
• Stem Cell Biology
• Molecular Signaling

Background:

• The signaling pathways governing gastric stem cell function remain largely uncharacterized.
• Understanding these pathways is critical for comprehending gastric homeostasis and disease pathogenesis.

Purpose of the Study:

• To investigate the role of Notch signaling in the regulation of LGR5(+) antral stem cells.
• To determine the effects of Notch pathway modulation on gastric stem and progenitor cell behavior and differentiation.

Main Methods:

• Utilized gastric organoid cultures and in vivo models for Notch pathway manipulation.
• Employed lineage tracing with multi-colored reporters and analyzed downstream signaling pathways like mTOR.

Main Results:

• Notch signaling is essential for LGR5(+) antral stem cell homeostasis, regulating proliferation and differentiation.
• Inhibition of Notch signaling reduced proliferation and promoted mucous/endocrine cell differentiation.
• Activation of Notch signaling increased proliferation, induced antral gland fission, and conferred a competitive advantage to stem cells, linking to mTOR signaling.

Conclusions:

• Notch signaling is a key intrinsic regulator of gastric epithelial stem cell function and tissue growth.
• Aberrant Notch activation in gastric stem cells drives hyper-proliferation and tissue expansion, potentially contributing to gastric tumorigenesis.