Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis

Lakshmikanth L. Chikkamenahalli; Erik Jessen; Cheryl E. Bernard; W.K. Eddie Ip; Margaret Breen-Lyles; Gianluca Cipriani; Suraj R. Pullapantula; Ying Li; Shefaa AlAsfoor; Laura Wilson; Kenneth L. Koch; Braden Kuo; Robert J. Shulman; Bruno P. Chumpitazi; Travis J. McKenzie; Todd A. Kellogg; James Tonascia; Frank A. Hamilton; Irene Sarosiek; Richard McCallum; Henry P. Parkman; Pankaj J. Pasricha; Thomas L. Abell; Gianrico Farrugia; Surendra Dasari; Madhusudan Grover

iScience (Mar 2024)

Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis

Lakshmikanth L. Chikkamenahalli,
Erik Jessen,
Cheryl E. Bernard,
W.K. Eddie Ip,
Margaret Breen-Lyles,
Gianluca Cipriani,
Suraj R. Pullapantula,
Ying Li,
Shefaa AlAsfoor,
Laura Wilson,
Kenneth L. Koch,
Braden Kuo,
Robert J. Shulman,
Bruno P. Chumpitazi,
Travis J. McKenzie,
Todd A. Kellogg,
James Tonascia,
Frank A. Hamilton,
Irene Sarosiek,
Richard McCallum,
Henry P. Parkman,
Pankaj J. Pasricha,
Thomas L. Abell,
Gianrico Farrugia,
Surendra Dasari,
Madhusudan Grover

Affiliations

Lakshmikanth L. Chikkamenahalli: Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
Erik Jessen: Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
Cheryl E. Bernard: Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
W.K. Eddie Ip: Department of Immunology, Mayo Clinic, Rochester, MN, USA
Margaret Breen-Lyles: Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
Gianluca Cipriani: Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
Suraj R. Pullapantula: Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
Ying Li: Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
Shefaa AlAsfoor: Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
Laura Wilson: Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
Kenneth L. Koch: Wake Forest University, Winston-Salem, NC, USA
Braden Kuo: Massachusetts General Hospital, Boston, MA, USA
Robert J. Shulman: Baylor College of Medicine, Houston, TX, USA
Bruno P. Chumpitazi: Duke University, Durham, NC, USA
Travis J. McKenzie: Department of Surgery, Mayo Clinic, Rochester, MN, USA
Todd A. Kellogg: Department of Surgery, Mayo Clinic, Rochester, MN, USA
James Tonascia: Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
Frank A. Hamilton: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA
Irene Sarosiek: Texas Tech University Health Sciences Center, El Paso, TX, USA
Richard McCallum: Texas Tech University Health Sciences Center, El Paso, TX, USA
Henry P. Parkman: Temple University, Philadelphia, PA, USA
Pankaj J. Pasricha: Mayo Clinic, Scottsdale, AZ, USA
Thomas L. Abell: University of Louisville, Louisville, KY, USA
Gianrico Farrugia: Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
Surendra Dasari: Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
Madhusudan Grover: Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA; Corresponding author

Journal volume & issue: Vol. 27, no. 3
p. 108991

Abstract

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Summary: Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial genes and increased the expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in the activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis were upregulated. Patients with IG had a greater abundance of monocyte-like cells. These data further link immune dysregulation to the pathophysiology of gastroparesis.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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