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Network analysis of large-scale ImmGen and Tabula Muris datasets highlights metabolic diversity of tissue mononuclear phagocytes

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Item Type:Article
Title:Network analysis of large-scale ImmGen and Tabula Muris datasets highlights metabolic diversity of tissue mononuclear phagocytes
Creators Name:Gainullina, A. and Mogilenko, D.A. and Huang, L.H. and Todorov, H. and Narang, V. and Kim, K.W. and Yng, L.S. and Kent, A. and Jia, B. and Seddu, K. and Krchma, K. and Wu, J. and Crozat, K. and Tomasello, E. and Dress, R. and See, P. and Scott, C. and Gibbings, S. and Bajpai, G. and Desai, J.V. and Maier, B. and This, S. and Wang, P. and Aguilar, S.V. and Poupel, L. and Dussaud, S. and Zhou, T.A. and Angeli, V. and Blander, J.M. and Choi, K. and Dalod, M. and Dzhagalov, I. and Gautier, E.L. and Jakubzick, C. and Lavine, K. and Lionakis, M.S. and Paidassi, H. and Sieweke, M.H. and Ginhoux, F. and Guilliams, M. and Benoist, C. and Merad, M. and Randolph, G.J. and Sergushichev, A. and Artyomov, M.N.
Abstract:The diversity of mononuclear phagocyte (MNP) subpopulations across tissues is one of the key physiological characteristics of the immune system. Here, we focus on understanding the metabolic variability of MNPs through metabolic network analysis applied to three large-scale transcriptional datasets: we introduce (1) an ImmGen MNP open-source dataset of 337 samples across 26 tissues; (2) a myeloid subset of ImmGen Phase I dataset (202 MNP samples); and (3) a myeloid mouse single-cell RNA sequencing (scRNA-seq) dataset (51,364 cells) assembled based on Tabula Muris Senis. To analyze such large-scale datasets, we develop a network-based computational approach, genes and metabolites (GAM) clustering, for unbiased identification of the key metabolic subnetworks based on transcriptional profiles. We define 9 metabolic subnetworks that encapsulate the metabolic differences within MNP from 38 different tissues. Obtained modules reveal that cholesterol synthesis appears particularly active within the migratory dendritic cells, while glutathione synthesis is essential for cysteinyl leukotriene production by peritoneal and lung macrophages.
Keywords:Myeloid Cells, Mononuclear Phagocytes, ImmGen, Network Analysis, Immunometabolism, Single-Cell RNA-seq, Animals, Mice
Source:Cell Reports
ISSN:2211-1247
Publisher:Cell Press / Elsevier
Volume:42
Number:2
Page Range:112046
Date:28 February 2023
Official Publication:https://doi.org/10.1016/j.celrep.2023.112046
PubMed:View item in PubMed

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