Dual ontogeny of disease-associated microglia and disease inflammatory macrophages in aging and neurodegeneration

Silvin A, Uderhardt S, Piot C, Da Mesquita S, Yang K, Geirsdottir L, Mulder K, Eyal D, Liu Z, Bridlance C, Thion MS, Zhang XM, Kong WT, Deloger M, Fontes V, Weiner A, Ee R, Dress R, Hang JW, Balachander A, Chakarov S, Malleret B, Dunsmore G, Cexus O, Chen J, Garel S, Dutertre CA, Amit I, Kipnis J, Ginhoux F (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Immunity Elsevier

Book Volume: 55

Pages Range: 1448-1465.e6

Journal Issue: 8

DOI: 10.1016/j.immuni.2022.07.004

Abstract

Brain macrophage populations include parenchymal microglia, border-associated macrophages, and recruited monocyte-derived cells; together, they control brain development and homeostasis but are also implicated in aging pathogenesis and neurodegeneration. The phenotypes, localization, and functions of each population in different contexts have yet to be resolved. We generated a murine brain myeloid scRNA-seq integration to systematically delineate brain macrophage populations. We show that the previously identified disease-associated microglia (DAM) population detected in murine Alzheimer's disease models actually comprises two ontogenetically and functionally distinct cell lineages: embryonically derived triggering receptor expressed on myeloid cells 2 (TREM2)-dependent DAM expressing a neuroprotective signature and monocyte-derived TREM2-expressing disease inflammatory macrophages (DIMs) accumulating in the brain during aging. These two distinct populations appear to also be conserved in the human brain. Herein, we generate an ontogeny-resolved model of brain myeloid cell heterogeneity in development, homeostasis, and disease and identify cellular targets for the treatment of neurodegeneration.

Authors with CRIS profile

Stefan Uderhardt Department of Medicine 3 – Rheumatology and Immunology Vasco Fontes Department of Medicine 3 – Rheumatology and Immunology

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

J087: Stromal Network Communication in the Regulation of Immune Homeostasis Jan. 16, 2021 - June 30, 2023

Involved external institutions

Singapore Immunology Network (SIgN) SG Singapore (SG) University of Virginia (UVA) US United States (USA) (US) Weizmann Institute of Science IL Israel (IL) Institut Gustave-Roussy FR France (FR) Shanghai Jiao Tong University / 上海交通大学 CN China (CN) École Normale Supérieure - PSL (ENS) FR France (FR) Analyse Moléculaire, Modélisation et Imagerie de la Maladie Cancéreuse (AMMICA) FR France (FR) NUS Yong Loo Lin School of Medicine SG Singapore (SG)

How to cite

APA:

Silvin, A., Uderhardt, S., Piot, C., Da Mesquita, S., Yang, K., Geirsdottir, L.,... Ginhoux, F. (2022). Dual ontogeny of disease-associated microglia and disease inflammatory macrophages in aging and neurodegeneration. Immunity, 55(8), 1448-1465.e6. https://doi.org/10.1016/j.immuni.2022.07.004

MLA:

Silvin, Aymeric, et al. "Dual ontogeny of disease-associated microglia and disease inflammatory macrophages in aging and neurodegeneration." Immunity 55.8 (2022): 1448-1465.e6.

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