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

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

Cell Reports

10.1016/j.celrep.2023.112046

https://doi.org/10.1016/j.celrep.2023.112046

Anastasiia Gainullina, Denis A. Mogilenko, Li-Hao Huang, Helena Todorov, Vipin Narang, Ki-Wook Kim, Lim Sheau Yng, Andrew Kent, Baosen Jia, Kumba Seddu, Karen Krchma, Jun Wu, Karine Crozat, Elena Tomasello, Regine Dress, Peter See, Charlotte Scott, Sophie Gibbings, Geetika Bajpai, Jigar V. Desai, Barbara Maier, Sébastien This, Peter Wang, Stephanie Vargas Aguilar, Lucie Poupel, Sébastien Dussaud, Tyng-An Zhou, Véronique Angeli, J. Magarian Blander, Kyunghee Choi, Marc Dalod, Ivan Dzhagalov, Emmanuel L. Gautier, Claudia Jakubzick, Kory Lavine, Michail S. Lionakis, Helena Paidassi, Michael H. Sieweke, Florent Ginhoux, Martin Guilliams, Christophe Benoist, Miriam Merad, Gwendalyn J. Randolph, Alexey Sergushichev, Maxim N. Artyomov

27 January 2023

Gainullina, A., Mogilenko, D. A., Huang, L.-H., Todorov, H., Narang, V., Kim, K.-W., Yng, L. S., Kent, A., Jia, B., Seddu, K., Krchma, K., Wu, J., Crozat, K., Tomasello, E., Dress, R., See, P., Scott, C., Gibbings, S., Bajpai, G., … Artyomov, M. N. (2023). Network analysis of large-scale ImmGen and Tabula Muris datasets highlights metabolic diversity of tissue mononuclear phagocytes. Cell Reports, 42(2), 112046. https://doi.org/10.1016/j.celrep.2023.112046

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.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

This work was supported by ImmGen Consortium grant AI072073 (NIAID, NIH) and in part by the Division of Intramural Research of the NIAID, NIH.

https://oar.a-star.edu.sg/communities-collections/articles/22580

2211-1247

Singapore Immunology Network

https://doi.org/10.1016/j.celrep.2023.112046