Serotonin-Expressing Cells in the Corpus of the Stomach Originate from Bone Marrow: A Master’s Thesis

Abstract

Neurogenin 3 and its downstream target NeuroD are basic helix-loop-helix transcription factors which promote endocrine differentiation in the gastrointestinal tract. However, mice lacking Ngn3 still produce several hormones in the stomach. Lineage tracing mouse models demonstrated that a majority of hormone cells in the corpus region of the stomach did not express Ngn3 or NeuroD during differentiation. Serotonin and histamine cells were entirely NeuroD-independently derived, and serotonin cells were additionally entirely Ngn3-independently derived. In this study, we isolated serotonin and histamine cells from the gastric corpus of transgenic mice expressing the fluorescent marker CFP. Serotonin cells expressed multiple mast cell markers by RT-PCR, and were found to be nearly absent in a mast cell-deficient mouse model. Labeled bone marrow transplant mice showed all serotonin cells derived from bone marrow. Histamine-expressing ECL cells, while lacking NeuroD, did not appear to express granulocyte or mast cell markers by analytical flow cytometry and RT-PCR, and resemble other enteroendocrine cell populations. Mouse gastric corpus serotonin cells, but not antral serotonin cells, are bone marrow-derived mast cells.