Network analysis of large-scale ImmGen and Tabula Muris datasets highlights metabolic diversity of tissue mononuclear phagocytes
Abstract
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.
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Licence : CC BY NC ND - Attribution - NonCommercial - NoDerivatives
Licence : CC BY NC ND - Attribution - NonCommercial - NoDerivatives