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

Autor:	Wogram E; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Sümpelmann F; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., 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., 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., Fernández Maestre I; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Fu D; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Braswell B; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., 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., Buescher JM; Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany., Mittler G; Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany., Borner GHH; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried 82152, Germany., Vlachos A; Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany., Tholen S; Institute of Surgical Pathology, Medical Center, University of Freiburg, 79106 Freiburg, Germany., Schilling O; Institute of Surgical Pathology, Medical Center, University of Freiburg, 79106 Freiburg, Germany., Bell GW; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Rambold AS; Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany., Akhtar A; Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany., Schnell O; Department of Neurosurgery, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Beck J; Department of Neurosurgery, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., 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., 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., 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.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2024 Sep 10; Vol. 57 (9), pp. 2216-2231.e11. Date of Electronic Publication: 2024 Aug 15.
DOI:	10.1016/j.immuni.2024.07.019
Abstrakt:	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 + ) generation in the cytoplasm. Our findings highlight the central role of phagosomes in microglial functioning in the healthy and diseased brain. Competing Interests: Declaration of interests R.J. is an advisor/co-founder of Fate Therapeutics and Fulcrum Therapeutics. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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