Premium
Gastric antral organoids are sustained by intrinsic Notch signaling (1119.1)
Author(s) -
Gifford Gail,
Demitrack Elise,
Spence Jason,
Simeone Diane,
Samuelson Linda
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1119.1
Subject(s) - organoid , notch signaling pathway , microbiology and biotechnology , stem cell , biology , epithelium , antrum , noggin , cell growth , signal transduction , stomach , biochemistry , gene , genetics , bone morphogenetic protein
The gastric epithelium undergoes constant turnover, with adult stem cells replenishing mature cell types to maintain homeostasis. The Notch signaling pathway is known to regulate gastric epithelial proliferation and differentiation, but little is known about mechanism. In this study we tested the hypothesis that Notch signaling is intrinsic to the epithelium and supports antral stem cell function. Mouse and human gastric organoids were used as a model to define epithelial Notch signaling. Organoids were established from antral glands and maintained in 3D culture in media containing EGF, Noggin, R‐spondin1 and Wnt3A. Gastric organoids were highly proliferative and contained differentiated gastric cell types, suggesting that they are sustained by antral stem cells. Notch pathway expression was determined by qRT‐PCR and function was tested using the Notch inhibitor DAPT. Pathway inhibition reduced cellular proliferation and organoid growth, and lowered the efficiency of organoid re‐establishment. Together these studies show that Notch signaling is intrinsically established by gastric epithelial cells in vitro to promote organoid proliferation and to maintain stem cell function. Grant Funding Source : Supported by NIH grants T32GM008322‐21/22 (GBG), T32DK094775‐02 (GBG), P01‐DK062041 (LCS)