Table 2.
Examples of transcriptomic studies to delineate homeostatic microglial genes in healthy mouse and human brain.
| Phenotype | Murine genes | Human genes | Methodology and tools |
|---|---|---|---|
| Homeostatic signature of microglia | Tgfbr1, Smad3, C1qa, C1qb, Cst3, Csf1r, Ctsd, Ctss, Cx3cr1, Entpd1, Fcrls, Hexb, Olfml3, P2ry12, Tmem119, Tmsb4x, Sparc, Lgmm, Tppp, Bin1, Rgs10, Gpr34, Sall1 |
P2RY12, P2RY13, C1QA, PROS1, GAS6, GPR34, MERTK, CX3CR1, TMEM119, CSFR1, SELPLG, MARCKS, AIF1, APBB1IP, ABI3, FCER1G |
Isolated cell populations from 2 month old C57BL/6 mice, CX3CR mice and Mr1-deficient mice22; miRNA array analysis and quantitative proteomic analysis of human microglia isolated from patients undergoing surgery22; scRNAseq of isolated microglia from 15 adults that underwent surgery for epilepsy or tumors26; Comparison of 9 published microglial signatures in human79 |
| microglia vs. myeloid populations |
Olfml2b, Cd34, Serpine2, Eya4, Lrrc3, Rtn4rl1, Slc46a1, Ccl12, Ccl4, Socs3, Sparc, Serpinf1, Rapgef5, Rtn1, Sema4d, Hexb, Arhgap22, Spata13, Hn1l, Hn1l, ll7r, Csmd3, Gpr84, Upk1b, St3gal6, H2-Oa, Trem2, Tmem204, Cables1, Cxxc5, Smad7, Ecscr, Ldhb, Ak1, Slc24a3, Slco4a1, Adora3, Fcrls, Fam46c, Olfml3, Slc2a5, Zfp691, Crybb1, Fscn1, Tmem119, Gal3st4, Siglech, Tmc7, Gpr56, Gas6, Sall1, Cx3cr1, Kcnd1, Tspan7, Gpr165 Transcription Factors: Bach2, Erf, Etv5, Junb, Jund, Klf12, Lmo2, Mycl1, Smad7, Sox4, Zfpm1, Zfp691 |
C1QA, C1QB, C1QC, GPR34 CCR2 absent in microglia |
Comparison of gene expression profiles - 6 week old C57BL/6J mice (Immunological Genome Project)23; RNAseq on ex vivo isolated microglia from 39 donors and 10 epilepsy surgery biopsies16; Profiling of isolated microglia from surgical- and autopsy-derived cortical brain samples47 |
| microglia vs. other CNS cells vs. macrophages | Olfml3, Tmem119, Siglech, Slc2a5, Gal3st4, Csmd3, Slco2b1, Gpr84, Lag3, F11r, Adora3, Ccl4, Golm1, P2ry13, Ccl3, Lrrc3, Egr1, Capn3, Tagap, Bco2, IL21r, Cx3cr1, Ccrl2, Grap, Fosb, Gtf2h2, Ptgs1 | CX3CR1, ITGAM, P2RY12, TYROBP | Whole brain transcriptome - C57BL/6 mice27; RNAseq on ex vivo isolated microglia from 39 donors and 10 epilepsy surgery biopsies16 |
| Microglia vs. macrophages | 95 genes in microglia but not macrophages 65 homeostatic genes, including Crybb1, Garnl3, Gpr34, Lag3, Nuak1, Olfml3, Rtn1, Rtn4rl1, Sall1, Sall3, Siglech, Slc1a3, Sparc, Tnfrsf17 |
1063 up- and 832 down-regulated (↑) B2M, MAPK6, ECM1, CSF1, SLC26A11 (↓) GARNL3, TMEM119, TLR10, TLR3, OLFML3, C3, CLEC17A, IGFSF10, BIN1, CX3CR1, P2RY12 |
C57BL/6 mice, 2 months old Cd11b+/Cd45low microglia5; RNAseq on human microglia from parietal cortex tissue and temporal lobe epilepsy surgery biopsies16 |
| microglial surfaceome | Slco4a1 , Slc30a5, Mcoln3, Lrp8, Lpact3, Stab1, Pap2c, Mfsd10, Cd40, Ketcap2, Tmem55b, Tmem48, Cmtm4 | No information available | Transcriptome of FACS-sorted cells – CX3CR1-GFP transgenic mice29 |
| microglial sensome | P2ry12, P2ry13, P2ry6, Gpr34, Adora3, Entpd1, Tmem173, P2yG, Csfr1, Csfr3, Tgfbr1, Tgfbr2, Ifngr1, Il10ra, Il6ra, Il21r, Tnfrsf17, Tnfrsf1b, Cx3cr1, Ccr5, C3ar1, Ptafr, Gpr77, Cmklr1, Cysltr1, Ccrl2, Cmtm6, C5ar1, Fcgr3, Fcer1g, Fcgr2b, Fcgr1, Cmtm7, Fcrl1, Fcgr4, Selplg, Ly86, Cd68, Trem2, Cd180, Tlr2, Cd37, Tlr7, Cd14, Clec4a3, Tlr4, Tlr13, Clec5a, havcr2, Clec7a, Cxcl16, Cd48, Ltf, Cd74, Uk1b, Tlr12, Tlr1, Pilra, Tlr6, Lfitm6, Itgam, Itgb2, Emr1, Ecscr, Lair1, Siglech, Slco2b1, Slc2a5, Lgals9, Gpr183, Tmem37, Cd33, Gpr84, Slc7a7, Cd52, Siglec5, Cd79b, Slc16a3, Icam1, Icam4, Cd94, Lag-3, Cd86, Ptprc, Dap12, Tnfrs13b, Tnfrsf17, Cd22, Tmem119, Cd53, Gi54, Slamf9, Clec4b1, Lilra5, Tmem8c, Gpr160, Cd101 | No information available | RNAseq - 5 month old C57BL/6 mice30 |
In bold, common microglial genes identified from transcriptomic studies.
To note: The discrimination between microglia, macrophages and infiltrating monocytes in human remains challenging partly due to the lack of reliable markers to distinguish these populations during the FACS isolation procedure.
Abbreviations: FACS, fluorescent cell sorting; sc, single cell.