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

Anastasiia Gainullina , Denis 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 (1, 2) , Elena Tomasello , Regine Dress , Peter See , Charlotte Scott , Sophie Gibbings , Geetika Bajpai , Jigar Desai , Barbara Maier , Sébastien This , Peter Wang , Stephanie Vargas Aguilar , Lucie Poupel , Sébastien Dussaud , Tyng-An Zhou , Veronique Angeli , J. Magarian Blander , Kyunghee Choi , Marc Dalod , Ivan Dzhagalov , Emmanuel Gautier (3) , Claudia Jakubzick , Kory Lavine , Michail Lionakis , Helena Paidassi , Michael Sieweke , Florent Ginhoux , Martin Guilliams , Christophe Benoist , Miriam Merad , Gwendalyn Randolph , Alexey Sergushichev , Maxim Artyomov

1 MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer
2 CIML - Centre d'Immunologie de Marseille - Luminy
3 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases

The diversity of mononuclear phagocyte (MNP) subpopulations across tissues is one of the key physiologicalcharacteristics of the immune system. Here, we focus on understanding the metabolic variability of MNPsthrough 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 ImmGenPhase I dataset (202 MNP samples); and (3) a myeloid mouse single-cell RNA sequencing (scRNA-seq) data-set (51,364 cells) assembled based on Tabula Muris Senis. To analyze such large-scale datasets, we developa network-based computational approach, genes and metabolites (GAM) clustering, for unbiased identifica-tion of the key metabolic subnetworks based on transcriptional profiles. We define 9 metabolic subnetworksthat encapsulate the metabolic differences within MNP from 38 different tissues. Obtained modules revealthat cholesterol synthesis appears particularly active within the migratory dendritic cells, while glutathionesynthesis is essential for cysteinyl leukotriene production by peritoneal and lung macrophages.

Keywords: CP: Immunology; CP: Metabolism; ImmGen; immunometabolism; mononuclear phagocytes; myeloid cells; network analysis; single-cell RNA-seq

Domains: Life Sciences [q-bio]

Anastasiia Gainullina, Denis Mogilenko, Li-Hao Huang, Helena Todorov, Vipin Narang, et al.. Network analysis of large-scale ImmGen and Tabula Muris datasets highlights metabolic diversity of tissue mononuclear phagocytes. Cell Reports, 2023, 42 (2), pp.112046. ⟨10.1016/j.celrep.2023.112046⟩. ⟨hal-04040831⟩