Microglia replacement by peripheral delivery of CSF1R inhibitor-resistant hematopoietic cells.

ABSTRACT: Microglia replacement holds great promise for the study and treatment of neurological diseases. We previously achieved high-efficiency replacement by engineering an inhibitor-resistant human CSF1R variant, G795A. Here and in Chadarevian et al, we introduce a transgenic mouse line carrying the homologous murine inhibitor resistance mutation, G793A. G793A confers resistance to CSF1R inhibitors (CSF1Ris) without impacting cell or organismal function, allowing brain-wide microglia replacement after intravascular delivery of myeloid cells or progenitors. G793A macrophages have normal CSF1R signaling and effector responses in cell-based assays. CSF1Ri treatment paired with peripheral vascular delivery of G793A myeloid cells, including ex vivo expanded hematopoietic stem cells, leads to microglia

SUBMITTER: Lombroso SI 

PROVIDER: S-EPMC12704446 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature