Figure 7. iMGLs transplanted into the brains of either wild-type or AD transplant competent mice are like brain microglia.

Within the brains of xenotransplantation compatible mice, transplanted iMGLs are ramified and interact with the neuronal environment. (A–L) After two months in vivo, iMGLs transplanted into mice display long-term viability with highly arborized processes resembling endogenous microglia found in the brain. (A) Transplanted iMGLs, labeled with P2ry12 (green; HPA HPA014518, Sigma) and human nuclei (ku80, red), exhibit long-term viability in mice. (B–D) At higher magnification, P2ry12 is highly expressed in iMGL arborized processes, both suggestive of homeostatic microglia surveying the brain environment. (E–H) Ramified iMGLs also express microglia-enriched Tmem119 recognized by a human-specific Tmem119 antibody (green; ab185333, Abcam, identified and validated in [Bennet et al, PNAS 2016], and human cytoplasm maker SC121 (hCyto, red). (I–L) At higher magnification, representative iMGLs express P2ry12 (green), hCyto (red), and Iba1 (blue; ab5076, Abcam). (M–P) Human iMGLs (hCyto,red) transplanted into AD-immune-deficient mice (Marsh et al, PNAS 2016) interact with and phagocytose amyloid plaques (white). (I–J) Transplanted iMGLs extend projections and migrate to plaques. iMGLs fully encompass amyloid plaques (O) and begin to phagocytose amyloid (P). Scale bars; (A,E,N) = 30 μm, (B–D, F–H, I–L, O,P) = 10 μm, (M) = 300 μm. n=3 animals per study. See also Figure S7.