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Microglia states and nomenclature: A field at its crossroads

Microglia states and nomenclature: A field at its crossroads
Microglia states and nomenclature: A field at its crossroads

Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as “resting versus activated” and “M1 versus M2.” This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions. To address these issues, we assembled a group of multidisciplinary experts to discuss our current understanding of microglial states as a dynamic concept and the importance of addressing microglial function. Here, we provide a conceptual framework and recommendations on the use of microglial nomenclature for researchers, reviewers, and editors, which will serve as the foundations for a future white paper.

0896-6273
3458-3483
Paolicelli, Rosa
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Sierra, Amanda
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Stevens, Beth
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Sierra, Amanda
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Stevens, Beth
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Audinat, Ettiene
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Butovsky, Oleg
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Cunningham, Colm
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Denes, Adam
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Eyo, Ukpong
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Garel, Sonia
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Ginhoux, Florent
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Hong, Soyon
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Miron, Veronique E.
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Molofsky, Anna Victoria
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Nadjar, Agnes
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Neumann, Harald
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Noda, Mami
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Peng, Bo
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Peri, Francesca
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Perry, V. Hugh
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Popovich, Phillip G.
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Priller, Josef
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Ragozzino, Davide
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Ransohoff, Richard M.
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Salter, Michael W.
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Schaefer, Anne
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Schafer, Dorothy P.
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Schwartz, Michal
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Simons, Mikael
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von Bernhardi, Rommy
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Wake, Hiroaki
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Wittamer, Valerie
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Wolf, Susanne A.
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Wu, Long-Jun
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Wyss-Coray, Tony
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Paolicelli, Rosa, Sierra, Amanda, Stevens, Beth, Tremblay, Marie-Eve, Aguzzi, Adriano, Ajami, Bahareh, Amit, Ido, Audinat, Ettiene, Bechmann, Ingo, Bennett, Mariko, Bennett, Frederick, Bessis, Alain, Biber, Knut, Bilbo, Staci, Blurton-Jones, Mathew, Boddeke, Erik, Brites, Dora, Brône, Bert, Brown, Guy C, Butovsky, Oleg, Carson, Monica J., Castellano, Bernardo, Colonna, Marco, Cowley, Sally A., Cunningham, Colm, Davalos, Dimitrios, De Jager, Philip L., de Strooper, Bart, Denes, Adam, Eggen, Bart J.L., Eyo, Ukpong, Galea, Elena, Garel, Sonia, Ginhoux, Florent, Glass, Christopher K., Gokce, Ozgun, Gomez-Nicola, Diego, González, Berta, Gordon, Siamon, Graeber, Manuel B., Greenhalgh, Andrew D., Gressens, Pierre, Greter, Melanie, Heneka, Michael, Heppner, Frank L., Hong, Soyon, Jung, Steffen, Kettenmann, Helmut, Kipnis, Jonathan, Koyama, Ryuta, Lemke, Greg, Lynch, Marina, Majewska, Ania, Malcangio, Marzia, Malm, Tarja, Mancuso, Renzo, Matteoli, Michela, McColl, Barry, Miron, Veronique E., Molofsky, Anna Victoria, Mracsko, Eva, Nadjar, Agnes, Neher, Jonas J., Neniskyte, Urte, Neumann, Harald, Noda, Mami, Peng, Bo, Peri, Francesca, Perry, V. Hugh, Popovich, Phillip G., Priller, Josef, Ragozzino, Davide, Ransohoff, Richard M., Salter, Michael W., Schaefer, Anne, Schafer, Dorothy P., Schwartz, Michal, Simons, Mikael, Streit, Wolfgang J., Tay, Tuan Leng, Verkhratsky, Alexei, von Bernhardi, Rommy, Wake, Hiroaki, Wittamer, Valerie, Wolf, Susanne A., Wu, Long-Jun and Wyss-Coray, Tony (2022) Microglia states and nomenclature: A field at its crossroads. Neuron, 110 (21), 3458-3483. (doi:10.1016/j.neuron.2022.10.020).

Record type: Article

Abstract

Microglial research has advanced considerably in recent decades yet has been constrained by a rolling series of dichotomies such as “resting versus activated” and “M1 versus M2.” This dualistic classification of good or bad microglia is inconsistent with the wide repertoire of microglial states and functions in development, plasticity, aging, and diseases that were elucidated in recent years. New designations continuously arising in an attempt to describe the different microglial states, notably defined using transcriptomics and proteomics, may easily lead to a misleading, although unintentional, coupling of categories and functions. To address these issues, we assembled a group of multidisciplinary experts to discuss our current understanding of microglial states as a dynamic concept and the importance of addressing microglial function. Here, we provide a conceptual framework and recommendations on the use of microglial nomenclature for researchers, reviewers, and editors, which will serve as the foundations for a future white paper.

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e-pub ahead of print date: 2 November 2022
Published date: 2 November 2022
Additional Information: Funding Information: All authors in the author list are listed in alphabetical order. This work was supported by grants from the Dementia Research Switzerland – Synapsis Foundation , Swiss National Science Foundation ( SNSF 310030_197940 ), and European Research Council ( ERC StGrant REMIND 804949 ) to R.C.P.; the Spanish Ministry of Science and Innovation Competitiveness MCIN/AEI/10.13039/501100011033 and FEDER “A way to make Europe” ( RTI2018-099267-B-I00 and RYC-2013-12817 ), a Tatiana Foundation award ( P-048-FTPGB 2018 ), and a Basque Government Department of Education project ( PIBA 2020_1_0030 ) to A.S.; Cure Alzheimer’s Fund and Alzheimer's Association to B.S.; the Canadian Institutes of Health Research (foundation grant 341846 , project grant 461831 ) and Natural Sciences and Engineering Research Council of Canada (discovery grant RGPIN-2014-05308 ) to M.E.T. M.E.T. is a Tier II Canada Research Chair in Neurobiology of Aging and Cognition. This work was also funded by DFG CRC/TRR167 “NeuroMac” to I.A., J.P., M.P., and S.J. and by DFG SFB 1052, Project 209933838 to I.B. Australian Research Council support for project DP150104472 to M.B.G. is gratefully acknowledged. Funding Information: B.A. is the shareholder and member of scientific advisory board of Tranquis Therapeutics. K.B. is an employee and shareholder of AbbVie. M.C. receives research support from Vigil, is a member of the scientific advisory board of Vigil, and has a patent on TREM2. S.C. is a recipient of research funding from Eli Lilly and Company. C.C. is a member of the advisory board of Exalys Therapeutics and is the recipient of a research grant from IONIS therapeutics. B.D.S. is occasionally consulting for different companies. He is founding scientist of Augustin TX and of Muna TX. He is also shareholder of Muna TX. C.H. collaborates with Denali Therapeutics. C.H. is chief advisor of ISAR Bioscience and a member of the advisory board of AviadoBio. J.K. is a scientific advisor and collaborator with PureTech. T.M. is a cofounder of REGAIN Therapeutics, owner of a provisional patent on compositions and methods for treatment and/or prophylaxis of proteinopathies, and owner of a provisional patent on preventing or reverting abnormal amyloid deposition. R.M. has scientific collaborations with Alector, Nodthera, and Alchemab and is a consultant for Sanofi. B.M. has received consultancy fees from AstraZeneca. A. Sierra is a recipient of a research grant from Hoffmann La Roche. Publisher Copyright: © 2022 Elsevier Inc.

Identifiers

Local EPrints ID: 473182
URI: http://eprints.soton.ac.uk/id/eprint/473182
ISSN: 0896-6273
PURE UUID: 4a7b090c-96a0-4998-aba0-1a811aadb39a
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

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Date deposited: 11 Jan 2023 17:55
Last modified: 17 Mar 2024 07:35

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Contributors

Author: Rosa Paolicelli
Author: Amanda Sierra
Author: Beth Stevens
Author: Marie-Eve Tremblay
Author: Adriano Aguzzi
Author: Bahareh Ajami
Author: Ido Amit
Author: Ettiene Audinat
Author: Ingo Bechmann
Author: Mariko Bennett
Author: Frederick Bennett
Author: Alain Bessis
Author: Knut Biber
Author: Staci Bilbo
Author: Mathew Blurton-Jones
Author: Erik Boddeke
Author: Dora Brites
Author: Bert Brône
Author: Guy C Brown
Author: Oleg Butovsky
Author: Monica J. Carson
Author: Bernardo Castellano
Author: Marco Colonna
Author: Sally A. Cowley
Author: Colm Cunningham
Author: Dimitrios Davalos
Author: Philip L. De Jager
Author: Bart de Strooper
Author: Adam Denes
Author: Bart J.L. Eggen
Author: Ukpong Eyo
Author: Elena Galea
Author: Sonia Garel
Author: Florent Ginhoux
Author: Christopher K. Glass
Author: Ozgun Gokce
Author: Berta González
Author: Siamon Gordon
Author: Manuel B. Graeber
Author: Andrew D. Greenhalgh
Author: Pierre Gressens
Author: Melanie Greter
Author: Michael Heneka
Author: Frank L. Heppner
Author: Soyon Hong
Author: Steffen Jung
Author: Helmut Kettenmann
Author: Jonathan Kipnis
Author: Ryuta Koyama
Author: Greg Lemke
Author: Marina Lynch
Author: Ania Majewska
Author: Marzia Malcangio
Author: Tarja Malm
Author: Renzo Mancuso
Author: Michela Matteoli
Author: Barry McColl
Author: Veronique E. Miron
Author: Anna Victoria Molofsky
Author: Eva Mracsko
Author: Agnes Nadjar
Author: Jonas J. Neher
Author: Urte Neniskyte
Author: Harald Neumann
Author: Mami Noda
Author: Bo Peng
Author: Francesca Peri
Author: V. Hugh Perry
Author: Phillip G. Popovich
Author: Josef Priller
Author: Davide Ragozzino
Author: Richard M. Ransohoff
Author: Michael W. Salter
Author: Anne Schaefer
Author: Dorothy P. Schafer
Author: Michal Schwartz
Author: Mikael Simons
Author: Wolfgang J. Streit
Author: Tuan Leng Tay
Author: Alexei Verkhratsky
Author: Rommy von Bernhardi
Author: Hiroaki Wake
Author: Valerie Wittamer
Author: Susanne A. Wolf
Author: Long-Jun Wu
Author: Tony Wyss-Coray

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