Development of a Chimeric Model to Study and Manipulate Human Microglia In Vivo.

ABSTRACT: iPSC-derived microglia offer a powerful tool to study microglial homeostasis and disease-associated inflammatory responses. Yet, microglia are highly sensitive to their environment, exhibiting transcriptomic deficiencies when kept in isolation from the brain. Furthermore, species-specific genetic variations demonstrate that rodent microglia fail to fully recapitulate the human condition. To address this, we developed an approach to study human microglia within a surrogate brain environment. Transplantation of iPSC-derived hematopoietic-progenitors into the postnatal brain of humanized, immune-deficient mice results in context-dependent differentiation into microglia and other CNS macrophages, acquisition of an ex vivo human microglial gene signature, and responsiveness to both acute and ch

SUBMITTER: Hasselmann J 

PROVIDER: S-EPMC7138101 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature