Human-specific paralogs of SRGAP2 induce neotenic features of microglia structural and functional maturation.

ABSTRACT: Microglia play key roles in shaping synaptic connectivity during neural circuits development. Whether microglia display human-specific features of structural and functional maturation is currently unknown. We show that the ancestral gene SRGAP2A and its human-specific (HS) paralogs SRGAP2B/C are not only expressed in cortical neurons but are the only HS gene duplications expressed in human microglia. Here, using combination of xenotransplantation of human induced pluripotent stem cell (hiPSC)-derived microglia and mouse genetic models, we demonstrate that (1) HS SRGAP2B/C are necessary and sufficient to induce neotenic features of microglia structural and functional maturation in a cell-autonomous manner, and (2) induction of SRGAP2-dependent neotenic features of micro

SUBMITTER: Diaz-Salazar C 

PROVIDER: S-EPMC11230448 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature