Table 3.
Gene expression summary in naïve (one time exposure to LPS in vitro) and second hit (exposed once in vivo and second time in vitro) microglia.
| Relevance | Gene name (Common name) | Naïve microglia | Second hit control | Second hit | |
|---|---|---|---|---|---|
| Activated mitochondrial biogenesis | SLC2A4 | 6.386 | 8.911 | 0.821 | |
| PPARGC1A | 4.842 | 5.835 | 1.466 | ||
| Adipocytokine signaling pathway | CAMKK1 | −1.110 | 0.511 | −0.205 | |
| CAMKK2 | 0.660 | 1.206 | 0.453 | ||
| Adiponectin | ADIPOQ | 2.422 | 4.588 | 1.137 | |
| Adrenoceptor alpha 1A | ADRA1A | 2.572 | 4.687 | −0.471 | |
| AMPK signaling pathway | PRKAA1 | 0.169 | 0.218 | −0.643 | |
| PRKAA2 | 2.776 | 4.784 | 1.774 | ||
| PRKAB1 | −0.189 | −1.319 | −2.603 | ||
| PRKAB2 | 0.861 | 0.179 | 0.066 | ||
| PRKAG1 | −0.379 | −3.249 | −2.168 | ||
| PRKAG2 | −0.405 | −1.194 | −0.513 | ||
| PRKAG3 | −1.329 | 0.099 | −0.050 | ||
| B-cell development and survival | TNFSF13B (BAFF) | 2.562 | −0.955 | −1.823 | |
| Calcium binding protein 39 | CAB39 | 0.279 | −1.520 | −1.583 | |
| CAB39L | −0.076 | −1.092 | −1.106 | ||
| Esterase enzyme | ACHE | −0.036 | −0.978 | −0.698 | |
| BCHE | −0.475 | −3.197 | −1.782 | ||
| Fractalkine/CX3CR1 axis and biological signature of microglial cells | CX3CR1 | 2.017 | 3.079 | 0.880 | |
| CX3CL1 | 0.618 | −0.443 | 0.076 | ||
| ITGAM (CD11b) | 0.130 | −0.113 | −1.083 | ||
| IL1B | 7.578 | 1.766 | 0.726 | ||
| Fructose-1,6-Biphosphate | FBP | −0.792 | 1.465 | 4.057 | |
| Gluconeogenesis and glucolysis | ALDOA | −0.106 | −0.485 | 0.355 | |
| ALDOB | −1.659 | −1.842 | −2.033 | ||
| ALDOC | −0.266 | −0.717 | 0.328 | ||
| PFKP | −0.461 | −0.228 | 0.686 | ||
| GPI | −0.940 | −2.001 | −0.363 | ||
| Growth, proliferation, fate determination, development, immunity | ELAVL1 | −0.252 | −0.986 | −0.895 | |
| CCNA1 | 2.574 | 6.259 | 2.854 | ||
| CCNA2 | 0.143 | 0.098 | 0.686 | ||
| IRF9 (p48) | 0.407 | −1.286 | −0.641 | ||
| PIM1 | 3.108 | −0.815 | −2.762 | ||
| EP300 (CBP) | 0.784 | 0.638 | −1.094 | ||
| CREBBP (CBP) | 0.881 | 0.752 | −0.835 | ||
| CISH (CIS) | 7.170 | 2.217 | −2.097 | ||
| HDAC genes: potential epigenetic regulators | HDAC1 | 2.271 | 0.145 | 0.676 | |
| HDAC10 | −0.242 | −0.840 | 0.116 | ||
| HDAC11 | −0.214 | 0.867 | 0.812 | ||
| HDAC2 | −0.299 | −2.746 | −2.423 | ||
| HDAC3 | 0.045 | −0.692 | 0.321 | ||
| HDAC4 | 1.292 | 1.502 | −0.691 | ||
| HDAC5 | −0.869 | 0.333 | 0.501 | ||
| HDAC6 | −0.688 | −0.126 | −0.430 | ||
| HDAC7 | −0.109 | 0.643 | −0.486 | ||
| HDAC8 | 0.336 | −0.889 | −2.510 | ||
| HDAC9 | 0.732 | 1.556 | −1.816 | ||
| Increased FFA oxidation | CPT1A | −0.260 | 0.631 | 0.100 | |
| CPT1B | 0.496 | 1.140 | 0.304 | ||
| CPT1C | 0.608 | 0.315 | 0.503 | ||
| Inhibit cell growth and protein synthesis | RPS6KB1 | −0.078 | −1.659 | −1.444 | |
| RPS6KB2 | −0.569 | −1.900 | −0.634 | ||
| EIF4EBP1 | −0.822 | −2.609 | −1.533 | ||
| PPARG2 | −2.093 | −2.107 | −0.656 | ||
| Inhibit protein synthesis | EEF2 | −0.005 | 0.210 | 0.421 | |
| EEF2K | −0.394 | 0.208 | −0.321 | ||
| Initiators of the JAK-Stat pathway | JAK1 | 0.213 | −1.404 | −2.112 | |
| JAK2 | 2.289 | 0.000 | −1.430 | ||
| JAK3 | 2.965 | 2.121 | −0.920 | ||
| TYK2 | 0.948 | −0.296 | −0.929 | ||
| STAT1 | −0.136 | −0.825 | −0.563 | ||
| STAT2 | 1.276 | −1.321 | −2.852 | ||
| STAT3 | 0.660 | −2.050 | −0.889 | ||
| STAT5A | 3.365 | −0.188 | −2.798 | ||
| STAT5B | 1.554 | −0.436 | −1.093 | ||
| Insulin signaling pathway | IGF1 | 1.601 | 2.264 | 1.177 | |
| IGF1R | −0.125 | −0.489 | −0.838 | ||
| IRS1 | 1.241 | 2.665 | 0.344 | ||
| IRS4 | 4.420 | 7.086 | 1.953 | ||
| Iron metabolism and/or anti-inflammatory | HMOX1 | −2.686 | −4.462 | −4.303 | |
| NRF-2 | 0.855 | −1.235 | −1.225 | ||
| JNK/P38 MAPK | MAPK8 (JNK) | 0.544 | −2.918 | −1.173 | |
| MAPK9 (JNK) | −0.266 | −2.257 | −2.853 | ||
| MAPK10 (JNK) | 1.492 | 3.024 | −0.262 | ||
| MAPK12 (P38) | −0.905 | −0.708 | 0.458 | ||
| MAPK13 (P38) | 3.294 | 3.173 | 0.171 | ||
| MAPK14 (P38) | −0.848 | −0.612 | 0.113 | ||
| Leptin | LEP | 5.033 | 7.429 | −0.143 | |
| LRP phagocytosis signaling | LRP1B | 4.522 | 6.380 | 0.336 | |
| LRP2 | 4.860 | 6.571 | 1.410 | ||
| LRP6 | 1.052 | 1.850 | 0.157 | ||
| Lymphocyte adhesion, T-cell costimulation | ICAM-1 | 4.055 | −0.181 | −2.801 | |
| Lymphoid-tissue homing | CCL21 | 18.917 | 20.916 | 0.368 | |
| CCL19 | 5.439 | 5.328 | −0.321 | ||
| mTOR signaling pathway | RHEB | −0.257 | −3.516 | −2.292 | |
| AKT1S1 | 0.908 | −0.657 | −1.496 | ||
| MTOR | −0.107 | −0.234 | −1.066 | ||
| RPTOR | 0.298 | 0.361 | −0.625 | ||
| Myeloiesis and B-cell lymphopoiesis | CXCL12 (SDF-1alpha) | −0.545 | 1.552 | 0.268 | |
| NF-kB signaling and inflammation | RELB | 1.503 | −1.389 | −1.227 | |
| NFKB | 2.676 | −0.323 | −0.200 | ||
| NFKBIA | 2.578 | −1.934 | −1.546 | ||
| NFKB1 (p50) | 2.569 | −0.801 | −2.673 | ||
| RELA (p65) | −0.031 | −2.098 | −2.268 | ||
| PTGS2 | 5.166 | −0.609 | −2.168 | ||
| TNF | 4.990 | 0.028 | −2.743 | ||
| PTGS2 | 5.166 | −0.609 | −2.168 | ||
| IL8 | 4.779 | −2.847 | −3.988 | ||
| IL1B | 7.578 | 1.766 | 0.726 | ||
| TNFAIP3 | 2.628 | −0.542 | −3.162 | ||
| Nitric oxide (NO) and NO production | NOS1 | 6.201 | 8.416 | 1.233 | |
| NOS1AP | 0.386 | −0.599 | −1.393 | ||
| NOS2 | 5.951 | 3.039 | −1.958 | ||
| NOS3 | 5.266 | 7.637 | 1.112 | ||
| P53 | TP53 | −0.554 | −0.379 | −1.539 | |
| MDM4 | 3.489 | −13.081 | −1.120 | ||
| PIK3-Akt signaling pathway | PIK3CA | 0.018 | −1.584 | −1.561 | |
| PIK3CB | 1.793 | −0.972 | −1.750 | ||
| PIK3CG | 1.950 | 1.106 | −0.094 | ||
| PIK3R1 | 1.330 | −1.533 | −1.884 | ||
| PIK3R3 | 1.083 | 2.066 | −1.507 | ||
| PIK3R5 | 4.343 | 2.695 | −0.635 | ||
| PDPK1 | 0.915 | 0.946 | −0.606 | ||
| AKT2 | −0.335 | −0.857 | −1.328 | ||
| AKT3 | 0.350 | 0.104 | −1.292 | ||
| TSC1 | 1.099 | 0.940 | −0.386 | ||
| TSC2 | 0.219 | 0.587 | 1.182 | ||
| Quality control | TGFBR1 | 0.327 | 0.158 | −0.943 | |
| TGFβ | −0.419 | −1.798 | −0.690 | ||
| GFAP | −1.044 | −5.512 | −3.709 | ||
| ITGAM (CD11b) | 0.130 | −0.113 | −1.083 | ||
| CD40 | 4.656 | 2.831 | 1.352 | ||
| IBA1 (AIF1) | 0.060 | 0.208 | 0.956 | ||
| Serine/threonine kinase 11 | STK11 | −0.178 | −1.553 | −1.491 | |
| STE20-related kinase adaptor alpha | STRADA | −0.536 | −1.252 | −1.293 | |
| STRADB | −0.506 | −2.816 | −3.582 | ||
| Tak1 protein | MAP3K7 | −0.057 | −0.809 | −2.136 | |
| Toll-like receptor 4 | TLR4 | 0.807 | −2.451 | −3.749 | |
| LY96 (MD-2) | 1.213 | 0.263 | 0.340 | ||
| LBP | 4.472 | 5.990 | 0.172 | ||
| Transcription factors | C-JUN | 0.795 | −1.539 | −2.385 | |
| C-FOS (FOS) | −3.072 | −1.635 | −0.317 | ||
| NFKB | 2.676 | −0.323 | −0.200 | ||
| CREB1 | 0.782 | −0.228 | 0.190 | ||
| ATF4 (creb TF) | 0.968 | −0.319 | 0.163 | ||
| CEBPB (CEBP) | 0.586 | −0.993 | −1.451 | ||
Bold values correspond to a significant log2 fold change (padj < 0.1).
Differential analysis of the count data was done with the DESeq2 package; up regulated genes are highlighted in red and down regulated genes are highlighted in blue. Values in the column “naïve cells” correspond to fold change from the naïve controls (NC) to LPS-exposed microglia (NL). In the same way, we compared second hit control (SHC) to the NC. Fold changes are summarized in the column “second hit control.” Values in the “second hit” column represent the fold change from NL to second-hit, i.e., LPS re-exposed, (SHL) microglia.