EGF and BMPs Govern Differentiation and Patterning in Human Gastric Glands
| Autor: | Aki Imai-Matsushima, Thomas F. Meyer, Alice Anna Daddi, Jan Traulsen, Jürgen Ordemann, Jan Bornschein, Maria del Mar Reines-Benassar, Kristin Fritsche, Sarah Wölffling, Peter Malfertheiner, Francesco Boccellato, Volker Brinkmann, Lennart Pfannkuch, Richard Lisle, Christian Goosmann, Alexander Link, Monika Schmid |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Gastritis Atrophic Cellular differentiation Bone Morphogenetic Protein 4 Biology Gastrointestinal epithelium 03 medical and health sciences 0302 clinical medicine Parietal Cells Gastric Epidermal growth factor Gastric glands medicine Gastric mucosa Humans Cell Lineage Wnt Signaling Pathway Cells Cultured Body Patterning Chief Cells Gastric Hepatology Epidermal Growth Factor Gastroenterology Gene Expression Regulation Developmental Cell Differentiation Epithelial Cells Epithelium Cell biology Gastric chief cell Organoids Foveolar cell 030104 developmental biology medicine.anatomical_structure Cellular Microenvironment Gastric Mucosa 030211 gastroenterology & hepatology Carrier Proteins |
| Zdroj: | Gastroenterology |
| ISSN: | 1528-0012 |
| Popis: | Background & Aims The homeostasis of the gastrointestinal epithelium relies on cell regeneration and differentiation into distinct lineages organized inside glands and crypts. Regeneration depends on Wnt/β-catenin pathway activation, but to understand homeostasis and its dysregulation in disease, we need to identify the signaling microenvironment governing cell differentiation. By using gastric glands as a model, we have identified the signals inducing differentiation of surface mucus-, zymogen-, and gastric acid–producing cells. Methods We generated mucosoid cultures from the human stomach and exposed them to different growth factors to obtain cells with features of differentiated foveolar, chief, and parietal cells. We localized the source of the growth factors in the tissue of origin. Results We show that epidermal growth factor is the major fate determinant distinguishing the surface and inner part of human gastric glands. In combination with bone morphogenetic factor/Noggin signals, epidermal growth factor controls the differentiation of foveolar cells vs parietal or chief cells. We also show that epidermal growth factor is likely to underlie alteration of the gastric mucosa in the precancerous condition atrophic gastritis. Conclusions Use of our recently established mucosoid cultures in combination with analysis of the tissue of origin provided a robust strategy to understand differentiation and patterning of human tissue and allowed us to draw a new, detailed map of the signaling microenvironment in the human gastric glands. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|