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

被引:5
|
作者
Chikkamenahalli, Lakshmikanth L. [1 ]
Jessen, Erik [2 ]
Bernard, Cheryl E. [1 ]
Ip, W. K. Eddie [3 ]
Breen-Lyles, Margaret [1 ]
Cipriani, Gianluca [1 ]
Pullapantula, Suraj R. [1 ]
Li, Ying [2 ]
AlAsfoor, Shefaa [1 ]
Wilson, Laura
Koch, Kenneth L. [4 ]
Kuo, Braden [5 ,6 ]
Shulman, Robert J. [7 ]
Chumpitazi, Bruno P. [8 ]
McKenzie, Travis J. [9 ]
Kellogg, Todd A. [9 ]
Tonascia, James [4 ]
Hamilton, Frank A. [10 ]
Sarosiek, Irene [11 ]
McCallum, Richard [11 ]
Parkman, Henry P. [12 ]
J. Pasricha, Pankaj [13 ]
Abell, Thomas L. [14 ]
Farrugia, Gianrico [1 ]
Dasari, Surendra [2 ]
Grover, Madhusudan [1 ]
机构
[1] Mayo Clin, Div Gastroenterol & Hepatol, Enter Neurosci Program, Rochester, MN 55905 USA
[2] Mayo Clin, Biomed Stat & Informat, Rochester, MN USA
[3] Mayo Clin, Dept Immunol, Rochester, MN USA
[4] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA
[5] Wake Forest Univ, Winston Salem, NC USA
[6] Massachusetts Gen Hosp, Boston, MA USA
[7] Baylor Coll Med, Houston, TX USA
[8] Duke Univ, Durham, NC USA
[9] Mayo Clin, Dept Surg, Rochester, MN USA
[10] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA
[11] Texas Tech Univ, Hlth Sci Ctr, El Paso, TX USA
[12] Temple Univ, Philadelphia, PA USA
[13] Mayo Clin, Scottsdale, AZ USA
[14] Univ Louisville, Louisville, KY USA
关键词
MUSCULARIS MACROPHAGES; ADHESION; REVEALS; NEUROGASTROENTEROLOGY; DIFFERENTIATION; POLARIZATION; EXPRESSION; MONOCYTES; MOTILITY;
D O I
10.1016/j.isci.2024.108991
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:18
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