title: Distinct cellular origins for serotonin-expressing and enterochromaffin-like cells in the gastric corpus.
abstract: OBJECTIVE
  The alimentary tract contains a diffuse endocrine system comprising enteroendocrine cells that secrete peptides or biogenic amines to regulate digestion, insulin secretion, food intake, and energy homeostasis. Lineage analysis in the stomach revealed that a significant fraction of endocrine cells in the gastric corpus did not arise from Neurogenin3 (Neurog3)-expressing cells, unlike enteroendocrine cells elsewhere in the digestive tract. We aimed to isolate enriched serotonin-secreting and enterochromaffin-like (ECL) cells from the stomach and to clarify their cellular origin.
  
  
  METHODS
  We used Neurogenic differentiation 1 (NeuroD1) and Neurog3 lineage analysis and examined the differentiation of serotonin-producing and ECL cells in stomach tissues of NeuroD1-cre;ROSA(tdTom), tryptophan hydroxylase 1 (Tph1)-cyan fluorescent protein (CFP), c-Kit(wsh/wsh), and Neurog3Cre;ROSA(tdTom) mice by immunohistochemistry. We used fluorescence-activated cell sorting to isolate each cell type for gene expression analysis. We also performed RNA sequencing analysis of ECL cells.
  
  
  RESULTS
  Neither serotonin-secreting nor ECL cells of the corpus arose from cells expressing NeuroD1. Serotonin-secreting cells expressed a number of mast cell genes but not genes associated with endocrine differentiation; they did not develop in c-Kit(wsh/wsh) mice and were labeled with transplanted bone marrow cells. RNA sequencing analysis of ECL cells revealed high expression levels of many genes common to endocrine cells, including transcription factors, hormones, ion channels, and solute transporters but not markers of bone marrow cells.
  
  
  CONCLUSIONS
  Serotonin-expressing cells of the gastric corpus of mice appear to be bone marrow-derived mucosal mast cells. Gene expression analysis of ECL cells indicated that they are endocrine cells of epithelial origin that do not express the same transcription factors as their intestinal enteroendocrine cell counterparts.
authors: Division of Gastroenterology, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Hui Joyce
authors: HJ
authors: Li
authors: Division of Gastroenterology, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Brian
authors: B
authors: Johnston
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Daniel
authors: D
authors: Aiello
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Daniel R
authors: DR
authors: Caffrey
authors: Department of Medicine, Tufts Medical Center, Boston, Massachusetts.
authors: Maryann
authors: M
authors: Giel-Moloney
authors: Sacred Heart Hospital, Rome, Italy.
authors: Guido
authors: G
authors: Rindi
authors: Division of Gastroenterology, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts. Electronic address: andrew.leiter@umassmed.edu.
authors: Andrew B
authors: AB
authors: Leiter
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D004759:Enterochromaffin Cells / Q000378:metabolism / Q000473:pathology*; D019858:Enteroendocrine Cells / Q000378:metabolism / Q000473:pathology*; D005753:Gastric Mucosa / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013270:Stomach / Q000473:pathology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D012701:Serotonin; C501008:Neurod1 protein, mouse; C407737:Neurog3 protein, mouse
keywords: Enterochromaffin-like Cell; Histidine Decarboxylase; NeuroD1; Serotonin