Figure 1. Mice may be generated with striata chimeric for human HD ESC-derived glia.
The striata of neonatally engrafted rag1 null mice were efficiently colonized with donor hESC hGPCs, a proportion of which differentiated as astroglia in both striatal grey and white matter. (a) Mice engrafted with hESC GPCs expressing either normal Htt (GENEA19; 18Q) or mHtt (GENEA20, 48Q; a sibling to GENEA19) manifested striatal chimerization by 20 weeks of age, which was denser at 40 weeks. Mice engrafted with GENEA20-derived glia (48Q) manifested striatal chimerization analogous to that of GENEA19-derived normal HTT (18Q) glia. (b) GENEA19-derived glia identified by their expression of the human-specific nuclear antigen (hNA; red) interspersed with host cells (DAPI, blue), revealing extent of striatal and cortical human glial chimerization at 40 weeks. (c,d) GENEA19 hGPC-engrafted striatal sections at 20 (c) and 40 (d) weeks post graft, stained for human and mouse NG2, showing the progressive domination of the striata by human NG2-defined GPCs. (e,f) 20 (e) and 40 (f) week post-graft striata, stained for hNA (red) and human PDGFRA (green) similarly showing the progressive domination of the striata by hGPCs. (g,h) GENEA19 hGPC-engrafted striata at 20 (g) or 40 (h) weeks, stained for hNA (red) human GFAP (green), showing the maturation and age-dependent increase in fibre complexity of human astroglia in the host striatum. Arrows indicate graft-derived OPCs (e,f) and astrocytes (g,h). Scale bars, 1 mm (a,b); 50 μm (c–g); 25 μm (h). DAPI, 4,6-diamidino-2-phenylindole.