An inducible genetic tool to track and manipulate specific microglial states reveals their plasticity and roles in remyelination.
Recent single-cell RNA sequencing studies have revealed distinct microglial states in development and disease. These include proliferative-region-associated microglia (PAMs) in developing white matter and disease-associated microglia (DAMs) prevalent in various neurodegenerative conditions. PAMs and DAMs share a similar core gene signature. However, the extent of the dynamism and plasticity of these microglial states, as well as their functional significance, remains elusive, partly due to the lack of specific tools. Here, we generated an inducible Cre driver line, Clec7a-CreERT2, that targets PAMs and DAMs in the brain parenchyma. Utilizing this tool, we profiled labeled cells during development and in several disease models, uncovering convergence and context-dependent differences in PAM and DAM gene expression. Through long-term tracking, we demonstrated microglial state plasticity. Lastly, we specifically depleted DAMs in demyelination, revealing their roles in disease recovery. Together, we provide a versatile genetic tool to characterize microglial states in CNS development and disease.
Pubmed ID: 38821054 RIS Download
Research resources used in this publication
- R Project for Statistical Computing (RRID:SCR_001905) (software resource)
- Adobe Illustrator (RRID:SCR_010279) (software resource)
- Imaris (RRID:SCR_007370) (software resource)
- B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax (RRID:MMRRC_034848-JAX) (organism)
- B6.129P2-Gt(ROSA)26Sortm1(DTA)Lky/J (RRID:IMSR_JAX:009669) (organism)
- B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J (RRID:IMSR_JAX:007909) (organism)
- Monocle3 (RRID:SCR_018685) (software resource)
- Seurat (RRID:SCR_016341) (software resource)
- Fiji (RRID:SCR_002285) (software resource)
- FlowJo (RRID:SCR_008520) (software resource)
- GraphPad Prism (RRID:SCR_002798) (software resource)
Additional research tools detected in this publication
None foundAntibodies used in this publication
- RAT ANTI MOUSE CD206 (RRID:AB_324622)
- Anti-Myelin Basic Protein Antibody (RRID:AB_2313550)
- Brilliant Violet 421(TM) anti-mouse/human CD11b (RRID:AB_10897942)
- Rat Anti-CD16 / CD32 Monoclonal Antibody, Unconjugated, Clone 2.4G2 (RRID:AB_394657)
- Donkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (RRID:AB_2534102)
- Donkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (RRID:AB_2536183)
- Hamster Anti-Mouse CD11c Monoclonal antibody, Unconjugated, Clone N418 (RRID:AB_324490)
- Anti-mDectin-1-IgG (RRID:AB_2753143)
- Pacific Blue(TM) anti-mouse CD19 (RRID:AB_439718)
- VECTASHIELD Mounting Medium with DAPI (RRID:AB_2336790)
- PE/Cyanine7 anti-mouse CD4 (RRID:AB_312706)
- PerCP/Cyanine5.5 anti-mouse CD19 (RRID:AB_2629815)
- Brilliant Violet 711(TM) anti-mouse MERTK (Mer) (RRID:AB_2876505)
- Brilliant Violet 650(TM) anti-mouse NK-1.1 (RRID:AB_2563159)
- APC anti-mouse/human CD11b (RRID:AB_312795)
- PE/Cyanine7 anti-mouse CX3CR1 (RRID:AB_2565699)
- Brilliant Violet 785(TM) anti-mouse CD206 (MMR) (RRID:AB_2565823)
- Brilliant Violet 421(TM) anti-mouse CD115 (CSF-1R) (RRID:AB_2562667)
- Brilliant Violet 785(TM) anti-mouse CD8a (RRID:AB_2562610)
- PE/Cyanine7 anti-mouse Tim-4 (RRID:AB_2565719)
- PerCP/Cyanine5.5 anti-mouse Ly-6C (RRID:AB_1659242)
- PerCP/Cyanine5.5 anti-mouse Ly-6G (RRID:AB_1877271)
- Brilliant Violet 421(TM) anti-mouse CD11c (RRID:AB_10897814)
- FITC anti-mouse Ly-6G (RRID:AB_1236488)
- Brilliant Violet 650(TM) anti-mouse F4/80 (RRID:AB_2564589)
- FITC anti-mouse I-A/I-E (RRID:AB_313321)
- APC/Cyanine7 anti-mouse CD45 (RRID:AB_312981)
- Brilliant Violet 711(TM) anti-mouse CD45 (RRID:AB_2564383)
- PE/Cyanine7 anti-mouse CD11c (RRID:AB_493569)
- Alexa Fluor 488-AffiniPure Donkey Anti-Mouse IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Rb,Rat,Shp Sr Prot) (RRID:AB_2341099)
- Alexa Fluor 488 AffiniPure Donkey Anti-Chicken IgY (IgG) (H+L) (RRID:AB_2340375)
- Donkey Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor ?? 488 Conjugated (RRID:AB_2535792)
- Brilliant Violet 711(TM) anti-mouse TCR beta chain (RRID:AB_2629564)
- Donkey anti-Goat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (RRID:AB_2535864)
- Alexa Fluor 647-AffiniPure Donkey Anti-Rat IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rb,Shp Sr Prot) (RRID:AB_2340694)
- Alexa Fluor 488-AffiniPure Donkey Anti-Rat IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Rb,Shp Sr Prot) (RRID:AB_2340683)
- CD31 Monoclonal Antibody (2H8) (RRID:AB_223592)
- Goat Anti-Rabbit IgG (H+L) Highly Cross-adsorbed Antibody, Alexa Fluor ?? 647 Conjugated (RRID:AB_141775)
- AQP1 (1) (RRID:AB_626692)
- Alexa Fluor(R) 488 anti-beta-Amyloid, 1-16 (RRID:AB_2564765)
- Recombinant Anti-CD68 antibody [EPR23917-164] (RRID:AB_2922954)
- ANTI-OLIG-2 (RRID:AB_570666)
- Iba1 antibody (RRID:AB_2224402)
Associated grants
- Agency: NIMH NIH HHS, United States
Id: R01 MH110504 - Agency: NCI NIH HHS, United States
Id: P30 CA091842 - Agency: NINDS NIH HHS, United States
Id: U19 NS123719 - Agency: NIA NIH HHS, United States
Id: R01 AG078512 - Agency: NIA NIH HHS, United States
Id: P01 AG078106
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This is a list of tools and resources that we have found mentioned in this publication.
RAT ANTI MOUSE CD206 (antibody)
RRID:AB_324622
This monoclonal targets RAT ANTI MOUSE CD206
View all literature mentionsAnti-Myelin Basic Protein Antibody (antibody)
RRID:AB_2313550
This polyclonal targets Myelin Basic Protein (MBP)
View all literature mentionsBrilliant Violet 421(TM) anti-mouse/human CD11b (antibody)
RRID:AB_10897942
This monoclonal targets CD11b
View all literature mentionsRat Anti-CD16 / CD32 Monoclonal Antibody, Unconjugated, Clone 2.4G2 (antibody)
RRID:AB_394657
This monoclonal targets CD16 / CD32
View all literature mentionsDonkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (antibody)
RRID:AB_2534102
This unknown targets IgG (H+L)
View all literature mentionsDonkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (antibody)
RRID:AB_2536183
This polyclonal secondary targets IgG (H+L)
View all literature mentionsHamster Anti-Mouse CD11c Monoclonal antibody, Unconjugated, Clone N418 (antibody)
RRID:AB_324490
This monoclonal targets Mouse CD11c
View all literature mentionsAnti-mDectin-1-IgG (antibody)
RRID:AB_2753143
This monoclonal targets Dectin-1
View all literature mentionsPacific Blue(TM) anti-mouse CD19 (antibody)
RRID:AB_439718
This monoclonal targets CD19
View all literature mentionsVECTASHIELD Mounting Medium with DAPI (antibody)
RRID:AB_2336790
This unknown targets
View all literature mentionsPE/Cyanine7 anti-mouse CD4 (antibody)
RRID:AB_312706
This monoclonal targets CD4
View all literature mentionsPerCP/Cyanine5.5 anti-mouse CD19 (antibody)
RRID:AB_2629815
This monoclonal targets CD19
View all literature mentionsBrilliant Violet 711(TM) anti-mouse MERTK (Mer) (antibody)
RRID:AB_2876505
This monoclonal targets MERTK
View all literature mentionsBrilliant Violet 650(TM) anti-mouse NK-1.1 (antibody)
RRID:AB_2563159
This monoclonal targets NK-1.1
View all literature mentionsAPC anti-mouse/human CD11b (antibody)
RRID:AB_312795
This monoclonal targets CD11b
View all literature mentionsPE/Cyanine7 anti-mouse CX3CR1 (antibody)
RRID:AB_2565699
This monoclonal targets CX3CR1
View all literature mentionsBrilliant Violet 785(TM) anti-mouse CD206 (MMR) (antibody)
RRID:AB_2565823
This monoclonal targets CD206
View all literature mentionsBrilliant Violet 421(TM) anti-mouse CD115 (CSF-1R) (antibody)
RRID:AB_2562667
This monoclonal targets CD115
View all literature mentionsBrilliant Violet 785(TM) anti-mouse CD8a (antibody)
RRID:AB_2562610
This monoclonal targets CD8a
View all literature mentionsPE/Cyanine7 anti-mouse Tim-4 (antibody)
RRID:AB_2565719
This monoclonal targets Tim-4
View all literature mentionsPerCP/Cyanine5.5 anti-mouse Ly-6C (antibody)
RRID:AB_1659242
This monoclonal targets Ly-6C
View all literature mentionsPerCP/Cyanine5.5 anti-mouse Ly-6G (antibody)
RRID:AB_1877271
This monoclonal targets Ly-6G
View all literature mentionsBrilliant Violet 421(TM) anti-mouse CD11c (antibody)
RRID:AB_10897814
This monoclonal targets CD11c
View all literature mentionsFITC anti-mouse Ly-6G (antibody)
RRID:AB_1236488
This monoclonal targets Ly-6G
View all literature mentionsBrilliant Violet 650(TM) anti-mouse F4/80 (antibody)
RRID:AB_2564589
This monoclonal targets F4/80
View all literature mentionsFITC anti-mouse I-A/I-E (antibody)
RRID:AB_313321
This monoclonal targets I-A/I-E
View all literature mentionsAPC/Cyanine7 anti-mouse CD45 (antibody)
RRID:AB_312981
This monoclonal targets CD45
View all literature mentionsBrilliant Violet 711(TM) anti-mouse CD45 (antibody)
RRID:AB_2564383
This monoclonal targets CD45
View all literature mentionsPE/Cyanine7 anti-mouse CD11c (antibody)
RRID:AB_493569
This monoclonal targets CD11c
View all literature mentionsAlexa Fluor 488-AffiniPure Donkey Anti-Mouse IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Rb,Rat,Shp Sr Prot) (antibody)
RRID:AB_2341099
This polyclonal targets Mouse
View all literature mentionsAlexa Fluor 488 AffiniPure Donkey Anti-Chicken IgY (IgG) (H+L) (antibody)
RRID:AB_2340375
This polyclonal targets IgY (IgG) (H+L)
View all literature mentionsDonkey Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor ?? 488 Conjugated (antibody)
RRID:AB_2535792
This unknown targets Rabbit IgG (H+L)
View all literature mentionsBrilliant Violet 711(TM) anti-mouse TCR beta chain (antibody)
RRID:AB_2629564
This monoclonal targets TCR beta chain
View all literature mentionsDonkey anti-Goat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (antibody)
RRID:AB_2535864
This polyclonal secondary targets IgG (H+L)
View all literature mentionsAlexa Fluor 647-AffiniPure Donkey Anti-Rat IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rb,Shp Sr Prot) (antibody)
RRID:AB_2340694
This unknown targets Rat IgG (H+L)
View all literature mentionsAlexa Fluor 488-AffiniPure Donkey Anti-Rat IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Rb,Shp Sr Prot) (antibody)
RRID:AB_2340683
This unknown targets Rat IgG (H+L)
View all literature mentionsCD31 Monoclonal Antibody (2H8) (antibody)
RRID:AB_223592
This monoclonal targets CD31
View all literature mentionsGoat Anti-Rabbit IgG (H+L) Highly Cross-adsorbed Antibody, Alexa Fluor ?? 647 Conjugated (antibody)
RRID:AB_141775
This unknown targets Rabbit IgG (H+L)
View all literature mentionsAlexa Fluor(R) 488 anti-beta-Amyloid, 1-16 (antibody)
RRID:AB_2564765
This monoclonal targets beta-Amyloid 1-16
View all literature mentionsRecombinant Anti-CD68 antibody [EPR23917-164] (antibody)
RRID:AB_2922954
This recombinant monoclonal targets CD68
View all literature mentionsANTI-OLIG-2 (antibody)
RRID:AB_570666
This polyclonal targets Oligodendrocute transcription factor 2
View all literature mentionsR Project for Statistical Computing (software resource)
RRID:SCR_001905
Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsAdobe Illustrator (software resource)
RRID:SCR_010279
Vector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.
View all literature mentionsImaris (software resource)
RRID:SCR_007370
Imaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.
View all literature mentionsB6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax (organism)
RRID:MMRRC_034848-JAX
Mus musculus with name B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax from MMRRC.
View all literature mentionsB6.129P2-Gt(ROSA)26Sortm1(DTA)Lky/J (organism)
RRID:IMSR_JAX:009669
Mus musculus with name B6.129P2-Gt(ROSA)26Sortm1(DTA)Lky/J from IMSR.
View all literature mentionsB6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J (organism)
RRID:IMSR_JAX:007909
Mus musculus with name B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J from IMSR.
View all literature mentionsMonocle3 (software resource)
RRID:SCR_018685
Software analysis toolkit for single cell RNA-seq. Used for single cell RNA-Seq experiments. Unsupervised algorithm that increases temporal resolution of transcriptome dynamics using single-cell RNA-Seq data collected at multiple time points.
View all literature mentionsSeurat (software resource)
RRID:SCR_016341
Software as R package designed for QC, analysis, and exploration of single cell RNA-seq data. Enable users to identify and interpret sources of heterogeneity from single cell transcriptomic measurements, and to integrate diverse types of single cell data.
View all literature mentionsFiji (software resource)
RRID:SCR_002285
Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsFlowJo (software resource)
RRID:SCR_008520
Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsGraphPad Prism (software resource)
RRID:SCR_002798
Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentions
