canonical myeloid ontology terms, supporting their use as surrogate for human microglia. Several individual genes were highly expressed in primary human fetal microglia and pMGLs, consistent with their identity (Suppl. Fig. 2a). Among those genes were CD11b (ITGAM), ITGB2, CSF1R, CD45, IBA1, ADORA3 or LGMN. In addition, pMGLs highly expressed genes relevant to nervous system disorders such as APOE, CD33 and TREM2 (Supplementary Fig. 2b). Likewise, HEXB, a causal gene for the lysosomal storage Sandhoff disease, was highly expressed in pMGLs, supporting the interest in microglial catabolism of GM2 ganglioside 32. Neural progenitors derived from the same pluripotent stem cells and further differentiated into complex cultures of neurons and glia (Diff. NPCs, see Fig. 6), express these genes to much lower levels (Fig. 5 and Supplementary Fig. 2), highlighting the lack of overlap between these mesodermal and neuro-ectodermal lineages, despite their side-by-side residence in the brain, in vivo.
