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

the NIDDK Gastroparesis Clinical Research Consortium (GpCRC)

doi:10.1016/j.isci.2024.108991

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

the NIDDK Gastroparesis Clinical Research Consortium (GpCRC)

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	108991
Journal	iScience
Volume	27
Issue number	3
DOIs	https://doi.org/10.1016/j.isci.2024.108991
State	Published - Mar 15 2024

Keywords

Gastroenterology
Immunology
Transcriptomics

ASJC Scopus subject areas

General

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10.1016/j.isci.2024.108991

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@article{047f767feec645809817af1e6f0af95f,

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

abstract = "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.",

keywords = "Gastroenterology, Immunology, Transcriptomics",

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

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = mar,

day = "15",

doi = "10.1016/j.isci.2024.108991",

language = "English (US)",

volume = "27",

journal = "iScience",

issn = "2589-0042",

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T1 - Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis

AU - the NIDDK Gastroparesis Clinical Research Consortium (GpCRC)

AU - Chikkamenahalli, Lakshmikanth L.

AU - Jessen, Erik

AU - Bernard, Cheryl E.

AU - Ip, W. K.Eddie

AU - Breen-Lyles, Margaret

AU - Cipriani, Gianluca

AU - Pullapantula, Suraj R.

AU - Li, Ying

AU - AlAsfoor, Shefaa

AU - Wilson, Laura

AU - Koch, Kenneth L.

AU - Kuo, Braden

AU - Shulman, Robert J.

AU - Chumpitazi, Bruno P.

AU - McKenzie, Travis J.

AU - Kellogg, Todd A.

AU - Tonascia, James

AU - Hamilton, Frank A.

AU - Sarosiek, Irene

AU - McCallum, Richard

AU - Parkman, Henry P.

AU - Pasricha, Pankaj J.

AU - Abell, Thomas L.

AU - Farrugia, Gianrico

AU - Dasari, Surendra

AU - Grover, Madhusudan

PY - 2024/3/15

Y1 - 2024/3/15

N2 - 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.

AB - 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.

KW - Gastroenterology

KW - Immunology

KW - Transcriptomics

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UR - http://www.scopus.com/inward/citedby.url?scp=85185453721&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2024.108991

DO - 10.1016/j.isci.2024.108991

M3 - Article

AN - SCOPUS:85185453721

SN - 2589-0042

VL - 27

JO - iScience

JF - iScience

IS - 3

M1 - 108991

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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