Hui Joyce Li1, Brian Johnston1, Daniel Aiello2, Daniel R Caffrey2, Maryann Giel-Moloney3, Guido Rindi4, Andrew B Leiter5. 1. Division of Gastroenterology, University of Massachusetts Medical School, Worcester, Massachusetts. 2. Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts. 3. Department of Medicine, Tufts Medical Center, Boston, Massachusetts. 4. Sacred Heart Hospital, Rome, Italy. 5. 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.
Abstract
BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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: Kristoffer L Egerod; Maja S Engelstoft; Kaare V Grunddal; Mark K Nøhr; Anna Secher; Ichiro Sakata; Jens Pedersen; Johanne A Windeløv; Ernst-Martin Füchtbauer; Jørgen Olsen; Frank Sundler; Jan P Christensen; Nils Wierup; Jesper V Olsen; Jens J Holst; Jeffrey M Zigman; Steen S Poulsen; Thue W Schwartz Journal: Endocrinology Date: 2012-10-12 Impact factor: 4.736
Authors: Josselin Soyer; Lydie Flasse; Wolfgang Raffelsberger; Anthony Beucher; Christophe Orvain; Bernard Peers; Philippe Ravassard; Julien Vermot; Marianne L Voz; Georg Mellitzer; Gérard Gradwohl Journal: Development Date: 2010-01 Impact factor: 6.868
Authors: Yu-cheng Wang; Marlene B Zuraek; Yasuhiro Kosaka; Yasuharu Ota; Michael S German; Evan S Deneris; Emily K Bergsland; David B Donner; Robert S Warren; Eric K Nakakura Journal: Endocr Relat Cancer Date: 2010-02-18 Impact factor: 5.678
Authors: M Sander; L Sussel; J Conners; D Scheel; J Kalamaras; F Dela Cruz; V Schwitzgebel; A Hayes-Jordan; M German Journal: Development Date: 2000-12 Impact factor: 6.868
Authors: Xiang Dong Yang; Walden Ai; Samuel Asfaha; Govind Bhagat; Richard A Friedman; Guangchun Jin; Heuijoon Park; Benjamin Shykind; Thomas G Diacovo; Andras Falus; Timothy C Wang Journal: Nat Med Date: 2010-12-19 Impact factor: 53.440
Authors: Fan Wang; Kaitlyn Knutson; Constanza Alcaino; David R Linden; Simon J Gibbons; Purna Kashyap; Madhusudan Grover; Richard Oeckler; Philip A Gottlieb; Hui Joyce Li; Andrew B Leiter; Gianrico Farrugia; Arthur Beyder Journal: J Physiol Date: 2016-08-13 Impact factor: 5.182
Authors: Josiane Fakhry; Martin J Stebbing; Billie Hunne; Yulia Bayguinov; Sean M Ward; Kent C Sasse; Brid Callaghan; Rachel M McQuade; John B Furness Journal: Cell Tissue Res Date: 2018-11-22 Impact factor: 5.249
Authors: Katilyn Knutson; Peter R Strege; Joyce Li; Andrew B Leiter; Gianrico Farrugia; Arthur Beyder Journal: J Vis Exp Date: 2018-09-26 Impact factor: 1.355
Authors: Mark D Borromeo; Trisha K Savage; Rahul K Kollipara; Min He; Alexander Augustyn; Jihan K Osborne; Luc Girard; John D Minna; Adi F Gazdar; Melanie H Cobb; Jane E Johnson Journal: Cell Rep Date: 2016-07-21 Impact factor: 9.423
Authors: Chaiyaboot Ariyachet; Alessio Tovaglieri; Guanjue Xiang; Jiaqi Lu; Manasvi S Shah; Camilla A Richmond; Catia Verbeke; Douglas A Melton; Ben Z Stanger; David Mooney; Ramesh A Shivdasani; Shaun Mahony; Qing Xia; David T Breault; Qiao Zhou Journal: Cell Stem Cell Date: 2016-02-18 Impact factor: 24.633