Rapid phagosome isolation enables unbiased multiomic analysis of human microglial phagosomes.

glioblastoma human pluripotent stem cells metabolomics microglia organelle phagocytosis phagosome proteomics quinolinic acid synaptic pruning

Journal

Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918

Informations de publication

Date de publication:
07 Aug 2024
Historique:
received: 17 09 2023
revised: 25 01 2024
accepted: 19 07 2024
medline: 17 8 2024
pubmed: 17 8 2024
entrez: 16 8 2024
Statut: aheadofprint

Résumé

Microglia are the resident macrophages of the central nervous system (CNS). Their phagocytic activity is central during brain development and homeostasis-and in a plethora of brain pathologies. However, little is known about the composition, dynamics, and function of human microglial phagosomes under homeostatic and pathological conditions. Here, we developed a method for rapid isolation of pure and intact phagosomes from human pluripotent stem cell-derived microglia under various in vitro conditions, and from human brain biopsies, for unbiased multiomic analysis. Phagosome profiling revealed that microglial phagosomes were equipped to sense minute changes in their environment and were highly dynamic. We detected proteins involved in synapse homeostasis, or implicated in brain pathologies, and identified the phagosome as the site where quinolinic acid was stored and metabolized for de novo nicotinamide adenine dinucleotide (NAD

Identifiants

DOI: 10.1016/j.immuni.2024.07.019 PMID: 39151426
pubmed: 39151426
pii: S1074-7613(24)00368-6
doi: 10.1016/j.immuni.2024.07.019
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests R.J. is an advisor/co-founder of Fate Therapeutics and Fulcrum Therapeutics.

Auteurs

Emile Wogram (E)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.

Felix Sümpelmann (F)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Wentao Dong (W)

Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; The Institute for Chemistry, Engineering & Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, CA 94305, USA.

Eshaan Rawat (E)

Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; The Institute for Chemistry, Engineering & Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, CA 94305, USA.

Inés Fernández Maestre (I)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Dongdong Fu (D)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Brandyn Braswell (B)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Andrew Khalil (A)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; The Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA; Harvard John A. Paulson School of Engineering and Applied Sciences, Boston, MA 02134, USA.

Joerg M Buescher (JM)

Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.

Gerhard Mittler (G)

Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.

Georg H H Borner (GHH)

Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.

Andreas Vlachos (A)

Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.

Stefan Tholen (S)

Institute of Surgical Pathology, Medical Center, University of Freiburg, 79106 Freiburg, Germany.

Oliver Schilling (O)

Institute of Surgical Pathology, Medical Center, University of Freiburg, 79106 Freiburg, Germany.

George W Bell (GW)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Angelika S Rambold (AS)

Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.

Asifa Akhtar (A)

Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.

Oliver Schnell (O)

Department of Neurosurgery, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.

Jürgen Beck (J)

Department of Neurosurgery, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.

Monther Abu-Remaileh (M)

Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; The Institute for Chemistry, Engineering & Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, CA 94305, USA.

Marco Prinz (M)

Institute of Neuropathology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies and Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, 79104 Freiburg, Germany.

Rudolf Jaenisch (R)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: jaenisch@wi.mit.edu.

Classifications MeSH