Table 1.
DEGs of major cell types from brainstem cell populations and enriched pathways compared with previous known ALS-related genes (Chia et al., 2018) and pathways (Krokidis and Vlamos, 2018; Poulin et al., 2016; Darmanis et al., 2015). Top DEGs (p < .01) and pathways, as well as those overlapping with previously reported AhS genes and pathways are shown.
| Cell type | No. of DEGs at p < .01 (DEGs at FDR < 5% in parenthesis) | Top 5 DEGs | Known ALS genes | Top enriched pathways from DEGs at p < .01; previously reported ALS-related pathways are in bold |
|---|---|---|---|---|
| Astrocytes | 864 (277) |
Up: Sod1, Mt1, Mt2, Fam107a
Down: Malat1 |
SOD1, PFN1, FUS, ATXN2 | neurogenesis, central nervous system development, head development, regulation of cell projection organization, neuron differentiation |
| Endothelial | 239 (17) |
Up: Sod1, Grid2, Rpl26, Creb3l3
Down: Gm4070 |
SOD1, VCP | interspecies interaction between organisms, regulation of multicellular organismal development, cell junction assembly, platelet degranulation, fc epsilon receptor signaling pathway |
| Ependymal | 35 (0) |
Up: Sod1, Ier3ip1, Cct3
Down: mt-Rnr2, Plac9a |
SOD1, PFN1 | negative regulation of smoothened signaling pathway, response to fluid shear stress, toxin transport, neurogenesis, osteoblast differentiation |
| Microglia | 227 (8) |
Up: Sod1, Camk2b
Down: Nav2, mt-Rnr2, 1700112E06Rik |
SOD1, VCP, ATXN2 | regulation of RAC protein signal transduction, positive regulation of molecular function, peptidyl lysine modification, intracellular signal transduction, immune system |
| Neurons1 | 102 (2) |
Up: Sod1
Down: Ctnna2, Astn2, Faf1, Ptprg |
SOD1 | synaptic signaling, regulation of dendritic spine morphogenesis, regulation of synaptic vesicle transport, cell-cell signaling, regulation of dendrite morphogenesis |
| Neurons2 | 223 (9) |
Up: Sod1, Grid2
Down: Sncg, Nefm, Lxn |
SOD1, NEFH, PFN1 | regulation of nervous system development, establishment of localization in cell, regulation of cell development, neurogenesis, positive regulation of cellular component organization |
| Schwann cells | 113 (5) |
Up: Sod1, Fth1
Down: Malat1, Reps2, Fopn1 |
SOD1 | neurogenesis, MET pathway, positive regulation of pri-miRNA transcription from RNA polymerase II promoter, regulation of neuron projection development, response to organophosphorus |
| MO | 685 (114) |
Up: Sod1, Sgk1, Grid2
Down: mt-Rnr2, Malat1 |
SOD1, VCP, FUS, MATR3, ATXN2, UBQLN2 | head development, neurogenesis, central nervous system development, ensheathment of neurons, protein localization to membrane |
| OPC | 229 (9) |
Up: Sod1
Down: Malat1, mt-Rnr2, Pcdh9, Lrrc4c |
SOD1, HNRNPA2B1, ATXN2, VCP, OPTN | neurogenesis, neuron cell cell adhesion, substantia nigra development, synapse organization, central nervous system development |
| VLMC | 209 (1) |
Up: Sod1
Down: Dcaf7, Slk, Abca8a, Col15a1 |
SOD1, MATR3 | protein localization to chromatin, collagen formation |
| unknown | 161 (7) |
Up: Sod1
Down: Fabp7, mt-Rnr2, Vim, Malat1 |
SOD1 | negative regulation of response to stimulus, negative regulation of multicellular organismal process, regulation of DNA templated transcription in response to stress, response to purine containing compound, negative regulation of protein metabolic process |
Note: MO – mature oligodendrocytes; OPC – oligodendrocyte precursor cells.