Cell Reports (Feb 2023)
Network analysis of large-scale ImmGen and Tabula Muris datasets highlights metabolic diversity of tissue mononuclear phagocytes
- 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,
- Veronique 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
Affiliations
- Anastasiia Gainullina
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Computer Technologies Department, ITMO University, St. Petersburg 197101, Russia; Laboratory of Bioinformatics and Molecular Genetics, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Moscow 119334, Russia
- Denis A. Mogilenko
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Department of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Li-Hao Huang
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
- Helena Todorov
- Laboratory of Immunoregulation, Inflammation Research Centre, VIB Ghent University, 9052 Ghent, Belgium
- Vipin Narang
- Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR), Singapore 138648, Singapore
- Ki-Wook Kim
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
- Lim Sheau Yng
- Immunology Translational Research Programme, Yong Loo Lin School of Medicine, Department of Microbiology and Immunology, National University of Singapore, Singapore 117545, Singapore; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore 117545, Singapore
- Andrew Kent
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA
- Baosen Jia
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA
- Kumba Seddu
- Department of Immunology, Harvard Medical School, Boston, MA 02115, USA
- Karen Krchma
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
- Jun Wu
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
- Karine Crozat
- Aix Marseille University, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living Systems, 13288 Marseille, France
- Elena Tomasello
- Aix Marseille University, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living Systems, 13288 Marseille, France
- Regine Dress
- Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR), Singapore 138648, Singapore
- Peter See
- Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR), Singapore 138648, Singapore
- Charlotte Scott
- Laboratory of Immunoregulation, Inflammation Research Centre, VIB Ghent University, 9052 Ghent, Belgium
- Sophie Gibbings
- Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA
- Geetika Bajpai
- Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA
- Jigar V. Desai
- Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Barbara Maier
- Immunology Institute and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Sébastien This
- Centre International de Recherche en Infectiologie (CIRI), University Lyon, Inserm, U1111, Université Claude Bernard Lyon ,1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France
- Peter Wang
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
- Stephanie Vargas Aguilar
- Aix Marseille University, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living Systems, 13288 Marseille, France; Center for Regenerative Therapies (CRTD), TU Dresden, 01307 Dresden, Germany; Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft (MDC), 13125 Berlin, Germany
- Lucie Poupel
- INSERM UMR-S 1166, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France
- Sébastien Dussaud
- INSERM UMR-S 1166, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France
- Tyng-An Zhou
- Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan
- Veronique Angeli
- Immunology Translational Research Programme, Yong Loo Lin School of Medicine, Department of Microbiology and Immunology, National University of Singapore, Singapore 117545, Singapore; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore 117545, Singapore
- J. Magarian Blander
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA
- Kyunghee Choi
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
- Marc Dalod
- Aix Marseille University, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living Systems, 13288 Marseille, France
- Ivan Dzhagalov
- Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan
- Emmanuel L. Gautier
- INSERM UMR-S 1166, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France
- Claudia Jakubzick
- Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA
- Kory Lavine
- Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA
- Michail S. Lionakis
- Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Helena Paidassi
- Centre International de Recherche en Infectiologie (CIRI), University Lyon, Inserm, U1111, Université Claude Bernard Lyon ,1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France
- Michael H. Sieweke
- Aix Marseille University, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living Systems, 13288 Marseille, France; Center for Regenerative Therapies (CRTD), TU Dresden, 01307 Dresden, Germany; Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft (MDC), 13125 Berlin, Germany
- Florent Ginhoux
- Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A∗STAR), Singapore 138648, Singapore
- Martin Guilliams
- Laboratory of Immunoregulation, Inflammation Research Centre, VIB Ghent University, 9052 Ghent, Belgium
- Christophe Benoist
- Department of Immunology, Harvard Medical School, Boston, MA 02115, USA
- Miriam Merad
- Immunology Institute and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Gwendalyn J. Randolph
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
- Alexey Sergushichev
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Computer Technologies Department, ITMO University, St. Petersburg 197101, Russia; Corresponding author
- Maxim N. Artyomov
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 2
p. 112046
Abstract
Summary: 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.
